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Ethnopharmacological Relevance: Positive deficiency and cancer toxicity are the main pathogenesis of colorectal cancer (CRC) lung metastasis. Yanghe decoction (YHD), a traditional Chinese medicine, has the effects of warming yang, tonifying blood, dispersing cold and clearing stagnation, adopting a treatment method that combines supporting the right and dispelling the wrong, which has remarkable efficacy in anti-tumor.Although, its precise mechanism of inhibiting the metastasis of colorectal cancer to the lung is still poorly understood., Aim of the Study: This study aimed to elucidate the antitumor properties of YHD within the context of colorectal cancer lung metastasis., Materials and Methods: Ultrahigh-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) was utilized to analyze the chemical composition of YHD. The anticancer activity of YHD was evaluated in a CRC lung metastasis mouse model by quantifying pulmonary metastatic nodules. The effects of YHD on CRC cell proliferation, apoptosis, cell cycle progression, and invasion were assessed using CCK-8 assays, flow cytometry, and Transwell assays. YHD-mediated immune modulation in tumor-bearing mice was evaluated by analyzing antitumor immunity, immunosuppressive cells, and cytokines in peripheral blood and tumor tissue. Gut microbiota analysis was conducted to determine the impact of YHD on the gut microbiota in mice., Results: Our analysis identified 1801 chemical markers in YHD. CFA exacerbated lung metastasis in CRC, whereas oral administration of YHD significantly mitigated this effect, as evidenced by the reduced number of metastatic lung nodules in CRC tumor-bearing mice. In vitro experiments demonstrated that YHD inhibits CRC cell proliferation, induces apoptosis, and suppresses invasion. In the lung tissues of mice with CRC metastasis treated with CFA, there was a significant reduction in NK cells and IL-21, along with an increase in M2 macrophages and IL-6. Following YHD treatment, there was a notable increase in NK cells and IL-21, accompanied by a decrease in M2 macrophages and IL-6 in lung tissues. YHD administration was also associated with an increase in beneficial bacterial species such as Bacillus and a decrease in deleterious bacterial species such as Oscillibacter., Conclusion: Our findings demonstrate that YHD inhibits lung metastasis in CRC by suppressing CRC cell proliferation and invasion, in addition to modulating the tumor microenvironment to favor antitumor immunity. These results provide a scientific basis for the clinical application of YHD in the treatment of CRC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Heterogeneous roles of complement C3 have been implicated in tumor metastasis and are highly context dependent. However, the underlying mechanisms linking C3 to tumor metastasis remain elusive in renal cell carcinoma (RCC). Here, we demonstrate that C3 of RCC cell-derived extracellular vesicles (EVs) contributes to metastasis via polarizing tumor-associated macrophages (TAMs) into the immunosuppressive phenotype and recruiting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, EV C3 induces the secretion of CCL2 and CXCL1 by lung macrophages and subsequently enhances TAM polarization and PMN-MDSC recruitment. Notably, targeting the CCL2/CCR2 or CXCL1/CXCR2 axis with the inhibitors RS504393 or Navarixin, respectively, effectively suppresses lung metastasis induced by RCC-derived C3 in a mouse model. Clinically, RCC patients with high expression of C3 demonstrate poor prognosis. Collectively, our findings reveal that tumor-derived EV C3 induces an immunosuppressive tumor microenvironment via TAMs, and thus promoting RCC metastasis., Competing Interests: Competing interests statement:The authors declare no competing interest.

Metastasis is complex and insidious type of disease involves multiple signaling nexus, which have implications in understanding disease pathogenesis. Treatment failure for metastatic cancer is frequently high due to aggressive adaptation of cancerous cells to invade to neighboring organs. Cytoskeleton intermediate filamentous protein Vimentin and scaffolding protein Neural precursor cell expressed Developmentally Down-regulated protein 9 (NEDD9) play a key role in metastatic events by regulating multiple metastatic events. Interaction between these proteins is necessary to promote metastatic progression. Withaferin A (WFA), a natural pharamacophore, known to target Vimentin to induce antitumor potential. However exact molecular mechanism still yet to be elucidated. We hypothesize, Vimentin-NEDD9 signaling nexus is necessary for metastatic progression and targeting this interwoven signaling loop with effective pharamacophore WFA halts metastatic progression of melanoma into lung. To elucidate the same, we carried out gene expression measurement through quantitative Reverses Transcription Polymerase Chain Reaction (qRT-PCR), Immunoblot and Immunohistochemistry. Assessment of interactive signaling by Co-immunoprecipitation, Immunofluorescence, Co-localization and Proximity ligation assay. Phosphorylation studies through transfection of phospho specific mutant constructs generated through site directed mutagenesis. WFA induced cellular behavioral changes by migration, invasion assays and Immunoblot analysis. The B16F10 induced mouse metastatic melanoma model to asses NEDD9-Vimentin expression and anti-metastasis induced by WFA. The results postulates, elevated levels and interaction between NEDD9-Vimentin proteins, have positive correlation in metastatic progression of melanoma into lung in both in-vitro and in-vivo condition, establishing it as therapeutic target. Pharmacologically, WFA targets this complex by extending its activity by not only inducing specific Serine 56 phosphorylation of Vimentin, also dissociates NEDD9 signaling loop to halt Epithelial-mesenchymal transition (EMT) and subsequent metastatic events. Eventually, modulation of the relevant metastatic genes E-Cadherin, N-Cadherin, SNAIL, MMP-2 & MMP-9 resulted in regression of metastatic melanoma progression to lung. The study validates WFA induced S56 phosphorylation is necessary to abrupt the NEDD9-Vimentin metastatic signaling complex to regress aggressive metastatic melanoma. The investigation emphasized more mechanistic approach of WFA. Understanding and targeting such integrative mechanical input in the tumor microenvironment will be a better therapeutic strategy to combat metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Carnosic acid is a naturally occurring, plant-derived polyphenolic abietane diterpene with antitumor properties. However, its underlying mechanisms are still unclear. Therefore, we investigated the effects of carnosic acid on lung metastasis in a murine melanoma model. C57BL/6 mice were intravenously injected with B16-BL6 cells, followed by carnosic acid treatment. Lung weights were recorded, and tumor cell colonies were counted at the end of the experiment. Integrin expression was evaluated using flow cytometry and cell adhesion assays. Lung weights were significantly lower in the carnosic acid group than in the control group, indicating the suppression of metastasis. Carnosic acid suppressed α4 integrin expression in B16-BL6 cells and inhibited α4 and α9 integrin-dependent cell adhesion. Thus, our data suggest that carnosic acid prevents lung metastasis, possibly by suppressing integrin expression. Our findings support the clinical application of carnosic acid as a potential natural antitumor agent, offering a complementary approach to conventional therapies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-γ production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors. Using a spontaneous metastasis mouse model of MHC-I + breast cancer, we found that transfer of IL-15/IL-12-conditioned syngeneic NK cells after primary tumor resection promoted long-term survival of mice with low metastatic burden and induced a tumor-specific protective T cell response that is essential for the therapeutic effect. Furthermore, NK cell transfer augments activation of conventional dendritic cells (cDCs), Foxp3 - CD4 + T cells and stem cell-like CD8 + T cells in metastatic lungs, to which IFN-γ of the transferred NK cells contributes significantly. These results imply direct interactions between transferred NK cells and endogenous cDCs to enhance T cell activation. We conducted an investigator-initiated clinical trial of autologous NK cell therapy in six patients with advanced cancer and observed that the NK cell therapy was safe and showed signs of effectiveness. These findings indicate that autologous NK cell therapy is effective in treating established low burden metastases of MHC-I + tumor cells by activating the cDC-T cell axis at metastatic sites., Competing Interests: SH, YL, HL, CC, RM, YC, YL, ZW, YW, KL, YH, JY, MD No competing interests declared, NL The following patent information is related to the work presented in this study. US9157068 B2: Formulation for cultivating dendritic killer cells and method using the same; US9597356 B2: Method for treating cancers with dendritic killer cells and pharmaceutical composition comprising the same; Applicant: Academia Sinica; Inventor: NSL, (© 2024, Huang, Lai, Liao et al.)

Purpose: Liver and lung metastases demonstrate distinct biological, particularly immunological, characteristics. We investigated whether preoperative complete blood count (CBC) parameters, which may reflect the immune system condition, predict early dissemination to the liver and lungs in colorectal cancer (CRC)., Methods: In this retrospective single-centre study, we included 268 resected CRC cases with complete 2-year follow-up and analysed preoperative CBC for association with early liver or lung metastasis development. Next, selected CBC and clinicopathological parameters were analysed with uni- and multivariable Cox regression. Independent factors affecting liver or lung metastasis-free survival were incorporated into composite scores, which were further evaluated with receiver operating characteristic (ROC) curves and dichotomised using a modified, specificity-focused, Youden approach to identify particularly high-risk patients., Results: Compared to metastasis-free patients, early liver metastases were related to decreases in red blood cells, haematocrit, lymphocytes and elevated monocyte-to-lymphocyte ratio, while lung metastases to lower eosinophil counts. A composite score of independent factors (erythrocytopenia, lower lymphocyte count and pN) yielded HR of 8.01 (95% CI 3.45-18.57, p < 0.001) for liver-specific metastasis-free survival (MFS). For lung-specific MFS, the combination of eosinopenia, pN and primary tumour location showed HR of 13.69 (95% CI 4.34-43.20, p < 0.001)., Conclusion: Early CRC metastases to the liver and lungs are associated with partially divergent clinicopathological and peripheral blood features. We propose simple, clinically implementable scores, based on routinely assessed parameters, to identify patients with an increased risk of early dissemination to the liver or lungs. After validation in independent cohorts, these scores may provide easily available prognostic information., Competing Interests: Declarations. Ethical approval: The study was approved by the Bioethical Committee of the Medical University of Gdańsk (NKBBN/688/2022). Competing interests: Marta Popęda, Jolanta Żok and Renata Duchnowska declare no financial conflict of interest. Bartłomiej Tomasik received lecture fees from Pfizer and honoraria from Roche. Michał Bieńkowski received lecture fees from Pfizer. All authors have no non-financial interests to disclose., (© 2025. The Author(s).)

Dendritic cells (DCs) play a crucial role in initiating antitumor immune responses. However, in the tumor environment, dendritic cells often exhibit impaired antigen presentation and adopt an immunosuppressive phenotype, which hinders their function and reduces their ability to efficiently present antigens. Here, a dual catalytic oxide nanosponge (DON) doubling as a remotely boosted catalyst and an inducer of programming DCs to program immune therapy is reported. Intravenous delivery of DON enhances tumor accumulation via the marginated target. At the tumor site, DON incorporates cerium oxide nanozyme (CeO 2 )-coated iron oxide nanocubes as a peroxide mimicry in cancer cells, promoting sustained ROS generation and depleting intracellular glutathione, i.e., chemodynamic therapy (CDT). Upon high-frequency magnetic field (HFMF) irradiation, CDT accelerates the decomposition of H 2 O 2 and the subsequent production of more reactive oxygen species, known as Kelvin's force laws, which promote the cycle between Fe 3+ /Fe 2+ and Ce 3+ /Ce 4+ in a sustainable active surface. HFMF-boosted catalytic DON promotes tumors to release tumor-associated antigens, including neoantigens and damage-associated molecular patterns. Then, the porous DON acts as an antigen transporter to deliver autologous tumor-associated antigens to program DCs, resulting in sustained immune stimulation. Catalytic DON combined with the immune checkpoint inhibitor (anti-PD1) in lung metastases suppresses tumors and improves survival over 40 days.

Acute upper limb ischaemia is a vascular emergency which requires prompt diagnosis and treatment to optimise outcomes. Tumour embolism is a rare but known cause of this. We hereby report a rare case of acute upper limb ischaemia from a malignant lung embolism, which was subsequently treated successfully with surgical embolectomy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Purpose: Immune checkpoint blockades (ICBs) are promising, however they do not fit all types of tumor, such as those lack of tumor antigens. Induction of potent anti-tumor T cell immunity is critical for cancer therapy. In this study, we investigated the efficacy of immunotherapy via the immunogenic cell death (ICD) dying tumor cells in mouse models of lung metastasis and tumorigenesis., Methods: ICD was induced by short exposure to lethal dose of chemotherapeutic drug doxorubicin (Dox), which initiated an irreversible ICD program in tumor cells. We immunized mice with ICD dying tumor cells in prevention, therapy in lung metastasis models, and Gprc5a-knockout (ko) model of lung tumorigenesis. T cells and macrophages isolated from lymph nodes or tumor tissues were analyzed by flow cytometry. Cytokines were analyzed by ELISA or Q-PCR analysis., Results: Immunization with these live but ICD dying tumor cells induced potent tumor-specific anti-tumor T cell immunity, which not only protected host from challenge by these tumor cells in prevention and therapy in mouse model of lung metastasis, but also prevented tumors development in Gprc5a-ko mouse model of lung tumorigenesis. The lymphocytes from lymph nodes and tumor tissues exhibited greatly enhanced activities of Th1 cells and M1 macrophages., Conclusion: Immunization with the ICD dying tumor cells evokes potent tumor-specific T cell immunity, which provides a novel approach for cancer immunotherapy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant bone cells coerce the lung microenvironment to support metastatic growth is unclear. The purpose of this study is to identify metastasis-specific therapeutic vulnerabilities by delineating the cellular and molecular mechanisms underlying osteosarcoma lung metastatic niche formation., Experimental Design: Using single-cell RNA sequencing, we characterized genome- and tissue-wide molecular changes induced within lung tissues by disseminated osteosarcoma cells in both immunocompetent murine models of metastasis and patient samples. We confirmed transcriptomic findings at the protein level and determined spatial relationships with multiparameter immunofluorescence and spatial transcriptomics. Based on these findings, we evaluated the ability of nintedanib, a kinase inhibitor used to treat patients with pulmonary fibrosis, to impair metastasis progression in both immunocompetent murine osteosarcoma and immunodeficient human xenograft models. Single-nucleus and spatial transcriptomics were used to perform molecular pharmacodynamic studies that define the effects of nintedanib on tumor and nontumor cells within the metastatic microenvironment., Results: Osteosarcoma cells induced acute alveolar epithelial injury upon lung dissemination. Single-cell RNA sequencing demonstrated that the surrounding lung stroma adopts a chronic, nonresolving wound-healing phenotype similar to that seen in other models of lung injury. Accordingly, the metastasis-associated lung demonstrated marked fibrosis, likely because of the accumulation of pathogenic, profibrotic, partially differentiated epithelial intermediates and macrophages. Our data demonstrated that nintedanib prevented metastatic progression in multiple murine and human xenograft models by inhibiting osteosarcoma-induced fibrosis., Conclusions: Fibrosis represents a targetable vulnerability to block the progression of osteosarcoma lung metastasis. Our data support a model wherein interactions between osteosarcoma cells and epithelial cells create a prometastatic niche by inducing tumor deposition of extracellular matrix proteins such as fibronectin that is disrupted by the antifibrotic tyrosine kinase inhibitor (TKI) nintedanib. Our data shed light on the non-cell-autonomous effects of TKIs on metastasis and provide a roadmap for using single-cell and spatial transcriptomics to define the mechanism of action of TKI on metastases in animal models., (©2024 The Authors; Published by the American Association for Cancer Research.)

Metastasis is the leading cause of mortality in cervical cancer (CC), with a particular prevalence of lymph node and lung metastases. Patients with CC who have developed distant metastases typically face a poor prognosis, and there is a scarcity of non-invasive strategies for predicting CC metastasis. In this study, we utilized label-free proteomics and untargeted metabolomics to analyze plasma samples from 25 non-metastatic, 14 with lung metastasis, and 15 with lymph node metastasis CC patients. Pathway enrichment analysis revealed a shared inflammatory process between the two metastatic groups, while the central carbon metabolism in cancer showed distinct features in the lung metastasis cohort. Additionally, cholesterol metabolism, hypoxia-inducible factor 1, and ferroptosis signaling pathways were specifically altered in the lymph node metastasis group. Utilizing the receiver operating characteristic curve analysis and Random Forest algorithm, we identified two distinct biomarker panels for the prediction of lung metastasis and lymph node metastasis, respectively. The lung metastasis panel includes properdin, neural cell adhesion molecule 1, and keratin 6 A, whereas the lymph node metastasis panel consists of quiescin sulfhydryl oxidase 1, paraoxonase 1, and keratin 6 A. Each panel exhibited significant diagnostic potential, with high area under the curve (AUC) values for lung metastasis (training set: 0.989, testing set: 0.789) and lymph node metastasis (training set: 0.973, testing set: 0.900). This study conducted an integrated proteomic and metabolomic analysis to clarify the factors contributing to lung and lymph node metastases in CC and has successfully established two biomarker panels for their prediction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rationale: The occurrence of refractory small cell lung cancer (rSCLC) with pancreatic metastasis is a relatively rare clinical condition, which is typically accompanied by a poor prognosis and rapid disease progression., Patient Concerns: A 65-year-old male farmer from China was diagnosed with limited-stage small cell lung cancer (SCLC) 8 months ago. Following 6 cycles of EP chemotherapy, the patient's tumor response showed partial relief. He discontinued chemotherapy for 2 months and subsequently experienced abdominal pain for 1 month., Diagnoses: A computed tomography scan revealed a malignant tumor in the lower lobe of the right lung, as well as low vascular nodules in the pancreas, which are suspected to be metastases. Laboratory tests indicated elevated levels of amylase and lipase, along with abnormalities in 5 indicators associated with lung cancer., Interventions: Upon admission, the patient received active treatment for pancreatitis. Given the progression of the tumor, salvage chemotherapy was initiated, combining albumin with paclitaxel and attilizumab, in consultation with a multidisciplinary team (MDT)., Outcomes: Abdominal pain was significantly reduced, and levels of amylase and lipase returned to normal, while neuron-specific enolase levels decreased. However, during subsequent follow-up, enlarged pancreatic lesions were identified, necessitating a reevaluation of treatment strategies., Lessons: This case study highlights the challenges associated with treating rSCLC that has metastasized to the pancreas. Although targeted therapy for metastasis-induced pancreatitis and systemic chemotherapy can alleviate symptoms and enhance patients' quality of life, continuous monitoring and optimization of treatment plans are essential for managing this aggressive disease. The findings emphasize the importance of a multidisciplinary approach in diagnosing and treating such complex cases, underscoring the necessity for personalized treatment strategies to address both the primary cancer and its metastatic complications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

The transforming growth factor β (TGF-β) signaling pathway exerts a dual role in oncogenesis, acting as a suppressor in healthy and early stage neoplastic tissues while promoting malignancy and metastasis in advanced cancers. Tumor hemorrhage further exacerbates TGF-β-mediated metastasis by up-regulating its expression. Here, a coagulation-targeting peptide (A15)-decorated TGF-β inhibitor nanomedicine (A15-LY-NPs) was developed. The tumor colonization assays showed that the nanomedicine reduced 4T1-luc cell colonization in normal tissues. When combined with a vascular disrupting agent, A15-LY-NPs demonstrated three times greater drug accumulation in the tumor at 24 h compared to the control and showed a 93.7% tumor suppression rate in 4T1 tumors initiated at ∼500 mm 3 , significantly attenuating metastatic spread to the lungs and liver. This study presents an innovative approach for the precise and efficient delivery of TGF-β inhibitors to tumors, offering the potential to augment the efficacy of cancer therapeutics.

Background: Metastasis is the primary cause of mortality in small cell lung cancer (SCLC), with the liver being a predominant site for distal metastasis. Despite this clinical significance, mechanisms underlying the interaction between SCLC and liver microenvironment, fostering metastasis, remain unclear., Methods: SCLC patient tissue array, bioinformatics analysis were performed to demonstrate the role of periostin (POSTN) in SCLC progression, metastasis, and prognosis. Cell migration, invasion and sphere formation assay were performed to determine the oncogenic role of POSTN. RNA sequencing analysis was utilized to identify the key signaling pathway regulated by POSTN. Immunoprecipitation, immunofluorescence and co-culture system were used to clarify the mechanism of POSTN-NOTCH1 axis in tumor cells-hepatic stellate cells (HSCs) crosstalk. Subcutaneous xenograft model and liver metastasis model were established to examine the anti-tumor growth and metastases effect of targeting POSTN-NOTCH1 signaling axis., Results: Elevated expression of POSTN in SCLC is correlated with accelerated tumor progression and metastasis. Conditioned medium rich in POSTN derived from SCLC tumors demonstrates the ability to activate HSCs in the liver microenvironment. Mechanistically, POSTN emerges as a binding partner for the membrane receptor NOTCH1 and transducing the extracellular signals to intracellular fibroblasts. Furthermore, targeting the POSTN-NOTCH1 signaling axis proves effective in suppressing SCLC tumor growth and inhibiting liver metastasis. This study elucidates that the SCLC-derived secreted protein POSTN interacts with NOTCH1 on HSCs to promote the activation of HSCs, thereby providing a favorable microenvironment for liver metastasis., Conclusion: These findings uncover the intricate communications between primary SCLC cells and HSCs in the tumor microenvironment mediated by the secreted protein POSTN in the context of liver metastasis. Consequently, targeting the POSTN-NOTCH1 signaling axis emerges as a promising therapeutic strategy for metastatic SCLC., Competing Interests: Declarations. Ethics approval and consent to participate: The animal procedures were approved by the Institutional Animal Care and Use Committee of Sun Yat-sen University and followed the Guide for the Care and Use of Laboratory Animals. Consent for publication: All authors have consented to the publication of this article. Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025. The Author(s).)

Introduction: Stage IV non-small cell lung carcinoma (NSCLC) with oligometastases is potentially curable by radical treatment. This study aimed to evaluate the efficacy and safety of chemoradiotherapy (CRT) for thoracic disease, including the primary lesion and lymph node metastases, combined with local consolidative therapy (LCT) for oligometastases., Methods: This was a multicenter Phase II trial for patients with Stage IV NSCLC with oligometastases for whom CRT for thoracic disease was feasible. The treatment procedures included CRT containing platinum-doublet for thoracic disease and LCT for oligometastases within 8 weeks of starting or completing CRT. The primary endpoint was the 2-year survival rate., Results: We enrolled 19 patients between June 2016 and May 2020. The median age was 68 (range: 51-74) years. Twelve patients had adenocarcinoma, and 6 had squamous cell carcinoma. The metastasis sites included the brain, bone, adrenal gland, lung, and cervical lymph node (n = 9, 7, 2, 1, and 1, respectively). All patients completed CRT concurrently with LCT for all oligometastases. There were 11 partial responses, resulting in a response rate of 58% (95% confidence interval [CI] 33.5-79.7%). Median progression-free survival and overall survival were 8.6 (95% CI 7.0-10.2) and 42.1 (80% CI 13.6-not reached) months, respectively. The 2-year survival rate was 68.4% (80% CI 52.6%-79.9%). Fourteen patients (74%) showed progression with newly observed lesions. There were no severe adverse events, and toxicities were tolerable., Conclusion: Chemotherapy in combination with aggressive LCT for NSCLC with oligometastases might extend survival and achieve local control., Clinical Trial Registration: University Hospital Medical Information Network, Japan (protocol identification number: UMIN000022431, first registration date: 01/JUN/2016)., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and Japan’s Clinical Trials Act. The protocol was registered with the University Hospital Medical Information Network, Japan (protocol identification number: UMIN000022431). All patients provided written informed consent. Consent for publication: All patients provided consent for publication. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This study aimed to identify radiotherapy dosimetric parameters related to local failure (LF)-free survival (LFFS) in patients with lung and liver oligometastases from colorectal cancer treated with stereotactic body radiotherapy (SBRT). We analyzed 75 oligometastatic lesions in 55 patients treated with SBRT between January 2014 and December 2021. There was no constraint or intentional increase in maximum dose. LF was defined as the progression of the treated lesion until the last follow-up or death. The dose distributions were recalculated using Monte Carlo-based algorithms. The significance of the planning target volume (PTV) biologically effective dose (BED) 10s (D2, D95, D98, Dmean) in LFFS was evaluated using Cox regression, considering sex, age, primary cancer, tumor site, oligometastatic status, multiplicity, and either tumor size or one of the volume parameters. LF occurred in 23.4% of the lesions. Lesions showing LF received significantly lower PTV D2 (146 ± 21 vs. 164 ± 23, p = 0.006). Multivariate analysis revealed that PTV D2 (< 159 Gy10 vs. ≥ 159 Gy10) was the sole dosimetric parameter associated with LFFS. Tumors equal to or larger than the median size/volume yet receiving < 159 Gy10 of PTV D2 showed the lowest LFFS following stratification by median PTV D2 combined with tumor size or volume parameters. The maximum dose (PTV D2) was significantly associated with LFFS after SBRT for lung and liver oligometastases from colorectal cancer. Increasing the maximum dose may be beneficial for managing larger tumors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale: Colorectal cancer (CRC) is a leading cause of cancer-related mortality. Epigenetic modifications play a significant role in the progression of CRC. KAT7, a histone acetyltransferase, has an unclear role in CRC. Methods: In this research, we analyzed the expression of KAT7 in CRC patients and its correlation with prognosis using the GEO database, western blot, and immunohistochemistry. We assessed the impact of KAT7 on CRC cell functions through cell viability, colony formation, flow cytometry, scratch, and transwell assays. Mechanistic insights were obtained via RNA sequencing and ChIP-qPCR. Additionally, we evaluated the effects of KAT7 on CRC growth and metastasis in vivo using mouse subcutaneous tumor and lung metastasis models. Results: In this study, we discovered an upregulated KAT7 signaling pathway in CRC and its association with poor patient survival. Knockdown of KAT7 promotes apoptosis and inhibits proliferation, migration, and invasion of CRC cells. Conversely, KAT7 overexpression enhanced these cellular processes. In vivo assays confirmed that knockdown of KAT7 can inhibit CRC proliferation and lung metastasis. Mechanistically, KAT7 acetylated histone H3 at lysine 14 (H3K14) to enhance MRAS transcription, which activated the MAPK/ERK pathway and promoted tumorigenesis. The enzymatic function of KAT7 as an acetyltransferase is crucial for the advancement of colorectal cancer. In KAT7 knockdown CRC cells, re-expression of KAT7, but not an acetyltransferase-deficient mutant, rescued MRAS expression, ERK phosphorylation, and CRC tumorigenesis. Conclusion: We found that KAT7 is highly expressed in CRC patients, and those with high KAT7 expression have a worse prognosis. KAT7 enhances MRAS gene transcription by promoting H3K14 acetylation, thereby activating the MAPK/ERK pathway and promoting malignant phenotypes of CRC. In summary, KAT7 represents a promising target for CRC therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Suppression of chimeric antigen receptor-modified T (CAR-T) cells by the immunosuppressive tumor microenvironment remains a major barrier to their efficacy against solid tumors. To address this, we develop an anti-PD-L1-expressing nanovesicle loaded with the STING agonist cGAMP (aPD-L1 NVs@cGAMP) to remodel the tumor microenvironment and thereby enhance CAR-T cell activity. Following pulmonary delivery, the nanovesicles rapidly accumulate in the lung and selectively deliver STING agonists to PD-L1-overexpressing cells via the PD-1/PD-L1 interaction. This targeted delivery effectively avoids the systemic inflammation and poor cellular uptake that plague free STING agonists. Internalized STING agonists trigger STING signaling and induce interferon responses, which diminish immunosuppressive cell populations such as myeloid-derived suppressor cells in the tumor microenvironment and promote CAR-T cell infiltration. Importantly, the anti-PD-L1 single chain variable fragment on the nanovesicle surface blocks PD-L1 upregulation induced by STING agonists and prevents CAR-T cell exhaustion. In both orthotopic lung cancer and lung metastasis model, combined therapy with CAR-T cells and aPD-L1 NVs@cGAMP potently inhibits tumor growth and prevents recurrence. Therefore, aPD-L1 NVs@cGAMP is expected to serve as an effective CAR-T cell enhancer to improve the efficacy of CAR-T cells against solid tumors., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Lung cancer is one of the leading causes of cancer-related deaths worldwide, with treatment failure resulting from metastasis. C-X-C chemokine receptor type 4 ( CXCR4 ) plays a crucial role in tumor cell migration and metastasis. Recent studies have suggested that the commonly used antiepileptic drug, carbamazepine (CBZ), may impede tumor metastasis; however, its specific mechanism remains unclear., Methods: In this study, we evaluated the effects of CBZ on the migration and invasion of lung cancer cells through in vitro cell cultures and in vivo animal models. The regulatory effect of CBZ on CXCR4 expression was analyzed using western blot and reverse transcription-quantitative polymerase chain reaction techniques. To further validate whether CBZ's anti-metastatic effect is mediated through CXCR4 , we used the CXCR4 agonist NUCC-390 and overexpression of the CXCR4 gene in lung cancer cell lines., Results: The results demonstrated that CBZ significantly inhibited the migration and invasion of lung cancer cells (* p < 0.001). In animal experiments, CBZ treatment significantly reduced the extent of metastasis in the lungs (* p < 0.01). Moreover, CBZ downregulated the expression of CXCR4 (* p < 0.001). When NUCC-390 was used or CXCR4 was overexpressed, the anticancer effect of CBZ was reversed, indicating the anti-metastatic effect of CBZ is closely associated with its inhibition of CXCR4 expression., Conclusion: This study reveals, for the first time, a novel mechanism by which CBZ inhibits lung cancer metastasis through the suppression of CXCR4 expression. These findings offer a new avenue for the treatment of lung cancer using CBZ as a potential agent against lung cancer metastasis. Further research is warranted to explore the clinical potential of CBZ and to offer more treatment options for lung cancer patients.

Aim: The lungs represent the second most common site of colorectal cancer metastases. Although surgery is commonly considered the best treatment, many other invasive and noninvasive procedures and treatments have been adopted to improve patient survival and there is no clear evidence in the literature of which is the more effective. The aim of this work was to identify which treatment confers the best gain in overall survival for patients with pulmonary metastases from colorectal cancer., Method: A systematic review and network meta-analysis of survival hazard ratio (HR) including 11 studies was conducted following the PRISMA guidelines and the Cochrane protocol on PubMed, Scopus, Embase, Web of Science and Cochrane Library up to 31 December 2023. Surgery, image-guided thermoablation, stereotactic body radiotherapy, chemotherapy and best standard care, associated or alone, were evaluated. Chemotherapy was adopted as the treatment reference to define survival HRs. Network metaregression was then performed considering patients with pulmonary only or multisite metastases from colorectal cancer., Results: In patients with pulmonary metastases, the association of surgery, stereotactic body radiotherapy and chemotherapy is the best performing (HR 0.22), while the most effective components alone are image-guided thermoablation (HR 0.53) and surgery (HR 0.57), although this was not significant. After metaregression, multimodal treatments still represent the strategy conferring the best survival gain. However, while surgery (incremental HR 0.26) has the most important role in patients with isolated pulmonary metastatic disease, chemotherapy (incremental HR 0.3) leads for patients with multimetastatic disease., Conclusion: Multimodal treatment confers the best gain in overall survival in patients with pulmonary metastases from colorectal cancer. Combining multiple therapeutic strategies improves survival, with oligometastatic patients benefiting more from surgery and local therapies while multimetastatic patients mainly benefit from chemotherapy, although ablation and surgery can enhance outcomes when feasible., (© 2025 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Lung cancer (LC) is a malignant tumor with high morbidity and mortality. Nearly 50% of patients with primary LC have distant metastases at the time of initial diagnosis. LC usually metastasizes from the lungs to the liver, adrenal glands, brain, and bone, but rarely to the gastrointestinal (GI) tract. Most gastrointestinal metastases (GIM) from LC are found on the basis of primary LC. GIM of LC with GI symptoms as the initial symptom is extremely rare. Moreover, the overall survival time of lung cancer patients developing intestinal metastases is from 5 weeks to 1 year, and most patients will die within the first 6 months. This report describes an uncommon case of lung adenocarcinoma that metastasized to the colon with initial symptoms involving the GI tract. After immunotherapy, the condition was stable for more than 2 years, and he is currently in good condition., (© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

The contemporary concept of carcinogenesis summarizes the role of hypoxia, neoangiogenesis, and hemostasis, including in the stage of progression and metastasis of the tumor process. Metastatic disease is a serious therapeutic challenge for any oncological condition. The purpose of this study was to evaluate the dynamics of specific indicators of neoangiogenesis and hypoxia as potential biomarkers for therapeutic efficacy or risk of disease progression in patients with brain metastases (BM) undergoing robotic stereotactic radiosurgery. Two groups of patients (lung cancer and other types of cancers) with oligometastatic disease and brain metastases were included. The patients (n = 66) were treated CyberKnife system. Human Angiopoietin-2, Hypoxia inducible factor 1 α (HIF-1α) and human Vascular Endothelial Growth Factor-А (VEGF-А) were measured in this prospective longitudinal study. Analysis of human Angiopoietin-2, HIF-1α, human VEGF-A in the post-treatment period showed a statistically significant decrease between the baseline and the 6 months post-treatment time point in both patient groups. The baseline value of serum VEGF-А in the group with lung cancer decreased by 40%, Аngiopoietin-2-by 48%, HIF-1α -by 43%. In the group with other types of cancers, VEGF-А decreased by 54.75%, Аngiopoietin-2-by 52%, HIF-1α -by 39.5%. Despite the significant reduction, the levels remained significantly higher in both groups than in healthy controls. This study underscores the potential of integrating molecular markers like VEGF-A, Angiopoietin-2, and HIF-1α into clinical decision-making to enhance outcomes for patients with brain metastases undergoing RSRS., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Metastasis is the major cause of cancer-related mortality. The premetastatic niche is a promising target for its prevention. However, the generality and cellular dynamics in premetastatic niche formation have remained unclear., Aims: This study aimed to elucidate the generality and cellular dynamics in premetastatic niche formation., Materials and Methods: We performed comprehensive flow cytometric analysis of lung and peripheral immune cells at three time points (early premetastatic, late premetastatic, and micrometastatic phases) for mice with subcutaneous implants of three types of cancer cells (breast cancer, lung cancer, or melanoma cells). The immuno-cell profiles were then used to predict the metastatic phase by machine learning., Results: We found a common pattern of changes in both lung and peripheral immune cell profiles across the three cancer types, including a decrease in the proportion of eosinophils in the early premetastatic phase, an increase in that of regulatory T cells in the late premetastatic phase, and an increase in that of polymorphonuclear myeloid-derived suppressor cells and a decrease in that of B cells in the micrometastatic phase. Machine learning using immune cell profiles could predict the metastatic phase with approximately 75% accuracy., Discussion: Validation of our findings in humans will require data on the presence or absence of micrometastases in patients and the accumulation of comprehensive and temporal information on immune cells. In addition, blood proteins, extracellular vesicles, DNA, RNA, or metabolites may be useful for more accurate prediction., Conclusion: The discovery of generalities in premetastatic niche formation allow prediction of metastatic phase and provide a basis for the development of methods for early detection and prevention of cancer metastasis in a cancer type-independent manner., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Increased survival can be achieved in patients with colorectal cancer peritoneal metastases (CRPM) treated with cytoreductive surgery. The benefit of this strategy remains uncertain when CRPM are associated with extraperitoneal metastases (EPM). The aim of this study was to compare short- and long-term outcomes of patients treated with CRS for CRPM, with or without EPM., Methods: This study included 413 consecutive patients who underwent CRS for CRPM: 120 with EPM (EPM+) and 293 without (EPM-). Patients with isolated ovarian metastases were included in EPM-group (n = 83)., Results: EPM were mainly located to the liver (66 %,n = 79), retroperitoneal lymph nodes (33 %,n = 40); less frequently to the spleen (9 %,n = 12), lung (9 %,n = 10) or pleura (1 %,n = 1). Ovarian metastases were present in 126 patients (83 in EMP-, 43 in EPM+). Peritoneal carcinomatosis index (PCI) was similar in EPM- (8 [4-14]) and EPM+ (8 [3-13],p = 0.335) groups, as postoperative mortality (3 % vs 3 %,p = 1) and major morbidity rates (28 % vs 35 %,p = 0.223). Median overall survival (mOS) and disease-free survival were significantly higher in the EPM-group (58m vs 39m, and 16m vs 10m,p = 0.003). We highlighted 3 prognostic groups 1) EPM-with PCI<10 (mOS 93m), 2) EPM+ with PCI<10 (mOS 57m), 3) EPM-with 1015 regardless EPM (mOS 26m, p < 0.001)., Conclusion: Complete cytoreductive surgery seems to be feasible in patients with EPM, without increase in postoperative morbidity and mortality compared to patients without EPM. This strategy provides prolonged survival in selected patients with limited peritoneal metastases from colorectal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Population-based data on the incidence of frequent colorectal metastases are fairly scarce, while that on rare metastatic sites are lacking., Aims: The aim of this study was to provide epidemiological indicators of metastatic sites frequency in patients with colorectal cancer., Methods: Incidence was modelled using Poisson and Joinpoint regressions in a population-based cancer registry study including metastatic colorectal cancers diagnosed between 1991 and 2020 (N = 5,199). Tumor molecular markers were collected for the [2016-2020] period., Results: Liver, peritoneum, lung and bone were the most frequent metastatic sites. Among frequent sites, incidence of liver and lung sites decreased in men respectively since 1999 and 2010, whereas in women incidence of liver and peritoneum sites increased steadily throughout the whole period. Each of the other sites concerned less than 3% of metastatic colorectal cancer cases and presented standardized incidence rates between 0.19 and 1.39 per 1,000,000. Among rare sites, incidence of adrenal glands, supraclavicular lymph node, mediastinum and ascites had doubled in [2016-2020] as compared to the 25 previous years. BRAFV600E variant was more frequent in presence of carcinomatosis, and absence of liver and lung metastasis while KRAS variant was more frequent in presence of lung metastasis., Conclusion: This study provides unprecedented incidence indicators for rare synchronous metastases of colorectal cancer., Competing Interests: Conflict of interest On behalf all authors, I declare that No potential conflicts of interest were disclosed., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Brain metastases (BMs) are the most common and among the deadliest brain tumors. Currently, there are no reliable predictors of BM development from primary cancer, which limits early intervention. Lung adenocarcinoma (LUAD) is the most common BM source and here we obtained 402 tumor and plasma samples from a large cohort of patients with LUAD with or without BM (n = 346). LUAD DNA methylation signatures were evaluated to build and validate an accurate model predicting BM development from LUAD, which was integrated with clinical factors to provide comprehensive patient-specific BM risk probabilities in a nomogram. Additionally, immune and cell interaction gene sets were differentially methylated at promoters in BM versus paired primary LUAD and had aligning dysregulation in the proteome. Immune cells were differentially abundant in BM versus LUAD. Finally, liquid biomarkers identified from methylated cell-free DNA sequenced in plasma were used to generate and validate accurate classifiers for early BM detection. Overall, LUAD methylomes can be leveraged to predict and noninvasively identify BM, moving toward improved patient outcomes with personalized treatment., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The tumor susceptibility gene 101 (TSG101) was firstly identified as a tumor-inhibiting factor in 1996. Subsequent studies gradually revealed its crucial role in several important cellular processes, including cell survival, vesicle transportation, viral infection, etc. Additionally, TSG101 has been identified as an oncoprotein in certain tumorigenic processes. These conflicting findings suggest that TSG101 might exhibit tumor heterogeneity. Currently, the expression pattern and function of TSG101 in oral squamous cell carcinoma (OSCC) are still untouched. Herein, we reported that TSG101 expression is upregulated and is associated with poorer survival and a higher propensity for lymph node metastasis in OSCC patients. In vivo mouse models confirmed that TSG101 down-regulation effectively inhibited the pulmonary metastases of human OSCC cells. In vitro cell experiments not only proved that TSG101 knockdown significantly disrupted metastasis-related phenotypes in different OSCC cell lines, but also revealed that TSG101 possibly controls the cell cycle through regulating the transcription of Cyclin A/B to play these roles. Additionally, we further validated these findings with a mouse cell line and murine orthotopic OSCC models. Collectively, the oncoprotein function of TSG101 in OSCC is evident from this study. We offer fresh insights into the heterogeneity of TSG101 and highlight new potential targets for OSCC management., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Trastuzumab deruxtecan (T-DXd) has demonstrated remarkable efficacy as a third- or later-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric and gastroesophageal junction adenocarcinomas. However, it may cause pneumonitis, and its efficacy in rare histologies such as gastric adenocarcinoma with enteroblastic differentiation (GAED) remains unclear. A 74-year-old woman with unresectable HER2-positive GAED and lung metastasis received T-DXd as a fifth-line chemotherapy. Treatment was discontinued after 15 cycles owing to drug-induced pneumonitis; however, the patient achieved a sustained complete response for 14 months without subsequent chemotherapy or the exacerbation of pneumonitis. T-DXd was effective in HER2-positive GAED.

Flurbiprofen axetil is commonly utilized in clinical practice as one of the nonsteroidal anti-inflammatory drugs (NSAIDs) and is included in multimodal analgesia regimens postbreast cancer surgery. Numerous NSAIDs have been studied for their potential to both promote and inhibit cancer. Given the variability in their effects on tumors, further investigation into the specific role of flurbiprofen axetil is warranted. Therefore, the primary objective of this study was to assess the impact of flurbiprofen axetil on basal-like breast cancer (BLBC) metastasis and elucidate the underlying molecular mechanisms involved. The BLBC metastasis mouse model was established by caudal vein injection of tumor cells. The lung metastasis of breast cancer in mice and the effect of flurbiprofen axetil were assessed by in vivo bioluminescence imaging, hematoxylin and eosin staining and immunohistochemistry. In vitro, the results of flurbiprofen axetil on the proliferation, migration, and invasion of MDA-MB-231 human breast cancer cells and BT-549 human breast cancer cells were assessed by colony formation assay and transwell assay. The effects of flurbiprofen axetil on several tumor metastasis-related signaling pathway proteins were examined by western blot, and the reversal extent of the flurbiprofen axetil effect by Ro 67-7476 (ERK phosphorylation agonist) was detected by transwell assay. The results showed that flurbiprofen axetil significantly inhibited BLBC lung metastasis in mice. Flurbiprofen axetil similarly inhibited breast cancer cell migration and invasion in vitro but did not affect their proliferation. Mechanistic investigations have revealed that flurbiprofen axetil exerts a noteworthy inhibitory influence on the MEK/ERK pathway while exhibiting no significant alteration in the expression of other pathway proteins intricately associated with epithelial-mesenchymal transition. In conclusion, the inhibitory effect of flurbiprofen axetil on BLBC metastasis is characterized by its selectivity in targeting the MEK/ERK signaling pathway rather than exerting a broad impact on the global signaling pathway., (© 2024 International Federation for Cell Biology.)

Background: Our objective was to elucidate the pivotal roles of BCAR1 in unfolded protein response (UPR), autophagy and vasculogenic mimicry (VM) formation, processes that essential for the metastasis of lung adenocarcinoma (LUAD) cells., Methods: The morphological assessment of endoplasmic reticulum (ER) status and autolysosomes in H1975 and H1299 LUAD cells following BCAR1 knockout (KO) was conducted using transmission electron microscope. The expression of markers and cellular functions related to the UPR, autophagy, and VM formation were examined in LUAD cells tissues. Additionally, proteomic analysis of LUAD cells was performed via mass spectrometry, and the pertinent signaling pathways were analyzed using bioinformatics tools., Results: BCAR1-KO inhibited autophagy and UPR induced triggered starvation in LUAD cells. Cleaved-ATF6a-mediated UPR and subsequent autophagy, enhanced by BCAR1, were confirmed using the UPR stimulator and blocker. High BCAR1 expression, along with elevated UPR and autophagy, predicts poor prognosis in LUAD patients. BCAR1-KO reduced tube formation and VM markers expressions in LUAD cells. Additionally, BCAR1 expression positively correlated with VM formation in BALB/c-nu mice xenografts and LUAD patient tissues., Conclusion: BCAR1 promotes LUAD metastasis by enhancing cancer cell survival in nutrient-poor environments through ATF6-mediated UPR activation and autophagy. As BCAR1 induces VM formation, metastatic lesions eventually colonize. Thus, BCAR1 is a promising anti-metastasis target., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Metastatic colorectal cancer (mCRC) is the main cause of CRC mortality, with limited treatment options. Although immunotherapy has benefited some cancer patients, mCRC typically lacks the molecular features that respond to this treatment. However, recent studies indicate that the immune microenvironment of mCRC may be modified to enhance the effect of immune checkpoint inhibitors. This study aimed to explore the metastatic tumor microenvironment (TME) by comparing cell populations in colorectal liver (CLM), lung (mLu), and peritoneal (PM) metastases., Methods: RNA isolated from 20 CLM, 15 mLu, and 35 PM samples was subjected to mRNA sequencing and explored through TME deconvolution tools, consensus molecular subtyping (CMS), and differential gene expression and gene set enrichment analysis, with respect to the metastatic sites. Clinical data and KRAS/BRAF hotspot mutation status were also obtained for all the cases., Results: The cell type fractions in the TME were relatively similar between the metastatic sites, except for cancer-associated fibroblasts (CAFs), B cells, endothelial cells, and CD4+ T cells. Notably, PM showed enrichment for CAFs and endothelial cells, consistent with distinct pathways associated with metastatic growth and progression in the peritoneal cavity. PM with the mesenchymal subtype, CMS4, had increased CAFs, endothelial cells, and macrophages, along with up-regulated genes related to TNF-α signaling via NF-κB, EMT, and angiogenesis., Conclusions: Tumor samples from different metastatic sites exhibited a broadly similar TME in terms of immune cell composition, with some intriguing differences. Targeting CAF-associated pathways, macrophages, and TNF-α signaling through NR4A could represent potential novel therapeutic approaches in CMS4 PM., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Lung metastasis is a critical and often fatal progression in cancer patients, with monocyte-derived macrophages (Mo-macs) playing multifaceted roles in this process. Despite the recognized importance of Mac-macs, most studies focus on these cells themselves, while the precise mechanisms through which tumor cells manipulate Mo-macs to promote metastasis remain poorly understood., Methods: We developed an in vivo CRISPR screening system to identify genes involved in macrophage-dependent metastasis by depleting Mo-macs. Osteoprotegerin (OPG) was identified as the factor significantly enhances lung metastasis. We validated its function in lung metastasis by modulating the expression of OPG in an array of cell lines and performed spontaneous and experimental lung metastasis assays. Genetically engineered mice were utilized to confirm the role of RANKL-RANK signaling in OPG-mediated metastasis. Additionally, we employed different neutralizing antibodies to elucidate the roles of Mo-macs and NK cells and inhibitor to clarify the role of CXCL10 signaling., Findings: Employing in vivo screening techniques, we elucidate the role of OPG, a protein secreted by cancer cells, in driving lung metastasis, contingent upon regulating Mo-mac activity. OPG blocks the signaling cascade between receptor activator of nuclear factor kappa-B ligand (RANKL) and its receptor RANK on Mo-macs, thereby hindering Mo-macs from secreting CXCL10, a chemokine crucial for recruiting natural killer (NK) cells that help control lung metastasis. Moreover, we observe an enrichment of OPG amplifications in metastatic cancer patients, and elevated levels of OPG expression in lung metastatic sites compared to paired primary breast cancer samples., Interpretation: Our work revealed that OPG works as a lung metastasis promoting factor by blocking the RANKL-RANK-CXCL10 axis to drive the paucity of NK cells, which could be a therapeutic target for lung metastatic cancer patients., Funding: The full list of funding supporting this study can be found in the Acknowledgements section., Competing Interests: Declaration of interests The authors declare no conflicts of interest in this study., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Prostate-specific membrane antigen (PSMA) Positron emission tomography/computed tomography (PET/CT) has become a crucial imaging modality for the staging of patients with prostate cancer. The purpose of this study is to retrospectively determine the frequency, anatomical distribution, and clinical-pathologic correlates of extra-nodal and extra-osseous metastatic prostate cancer detected on PSMA PET/CT., Methods: All available 650 PSMA PET/CT performed in patients with biopsy-proved prostate cancer in our institution between September 2021 and December 2023 were reviewed for the presence of extra-nodal and extra-osseous metastatic disease (M1C disease). Thirty-four patients with M1C disease were identified., Results: The most frequent sites of visceral/soft tissue metastases were the lungs (58.8%), liver (23.5%) and adrenal glands (20.6%). 75% of patients with lung metastases detected on PSMA PET/CT had concurrent intrathoracic lymph node involvement. A higher frequency of patients with M1C disease (55.9%) had a high Gleason score. The median prostate-specific antigen (PSA) level at the time of the PSMA scan was 20.16 ng/mL. There was a statistically significant association between PSA level and osseous disease (p = 0.004), as well as PSA level and nodal disease (p = 0.008). While a large number of patients had concurrent osseous and nodal disease (82.4% and 79.4%, respectively), no visceral/soft tissue sites demonstrated a significant association with the presence of osseous or nodal involvement., Conclusions: Given the increasing utilization of PSMA PET/CT, increased knowledge of the location and pattern of distribution of visceral/soft tissue metastatic sites is crucial not only for staging but also to better understand patterns of therapeutic response. We identified the lungs, liver and adrenal glands as the most common visceral/soft tissue metastatic sites from prostate cancer. We found that higher PSA levels at the time of PSMA PET/CT imaging were positively associated with concurrent osseous and nodal involvement., (© 2024 Wiley Periodicals LLC.)

The infiltration of cytotoxic T lymphocytes holds promise for suppressing even the most resilient metastatic tumors in immunotherapy. Polarizing tumor-associated macrophages (TAMs) and remodeling the immune-deficient tumor microenvironment (TME) can enhance T lymphocyte recruitment and infiltration. However, the immune privilege and low immunogenic responses of these aggressive tumor clusters often limit lymphocyte recruitment. Here, an M1 macrophage membrane-coated iron oxide nanoparticle (IO@MM) double as a tumor-penetrated agent and naïve M0 macrophage to M1 polarizer is developed for lung metastatic colorectal cancer (CRC) immunotherapy. At the tumor site, IO@MM combined with resiquimod (R848) increased the immune cell infiltration, turning the "Cold" TME into an immune-activating "Hot" one. Together with self-cascade immunotherapy, IO@MM with R848 promotes tumor release of damage-associated molecular patterns (DAMPs). At the same time, IO@MM uses the membrane as an antigen reservoir and provides autologous DAMPs to retain dendritic cells. This IO@MM effectively inhibits tumors and improves survival rate as an immunomodulator in lung metastasis., (© 2024 Wiley‐VCH GmbH.)

Background/aim: Metastatic patterns are the most convenient and common prediction models for the prognosis of patients with stage IV colorectal cancer. However, current prediction models do not include the severity of metastases in organs and exclude certain types of metastatic patterns. The aim of this study was to develop a prediction model that included several metastatic organs as well as the severity of liver and lung metastases, based on the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma: the 3 rd English Edition., Patients and Methods: We performed a state-wide cohort study and developed a prediction model using Cox proportional hazard regression analysis, utilizing data on patients with stage IV colorectal cancer in hospital-based cancer registries of all nine designated cancer hospitals across Fukushima Prefecture, Japan., Results: The study included 1,230 patients with stage IV colorectal cancer. The prediction score consisted of the severity of liver and lung metastases, peritoneal dissemination, non-regional lymph node metastases, and other organ metastases (scale: 0-9 on a 10-point scale; divided into a 2-point scale, grade: I-V). The study found that the model had good discrimination properties, with a Harrell's concordance index of 0.64 (95% confidence interval: 0.62-0.66), and the grade was an independent prognostic factor [hazard ratio (HR)=1.83; 95% confidence interval=1.68-2.00; p<0.001]., Conclusion: We created a practical prediction model for stage IV colorectal cancer that can be applied at the time of diagnosis, using only metastatic patterns. Further external validation studies are required to ensure the accuracy of this model., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Abstract: We present the 18 F-FDG PET/CT findings of a 64-year-old man with isolated renal metastasis. He had a history of radical surgery for squamous cell lung cancer 14 months ago, followed by chemotherapy and immunotherapy. The renal metastasis presented as a small focus of increased FDG uptake in the restaging 18 F-FDG PET/CT scan, which was regarded as renal cortical tracer retention. The renal metastasis was more prominent on the second PET/CT performed 5 months later. The patient subsequently underwent radical nephrectomy, and histopathological examination confirmed the diagnosis of renal squamous cell carcinoma metastasis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Management of suspected choroidal metastases requires diagnostic imaging and an invasive, sometimes intraocular, biopsy to determine the primary malignancy. This multistep process takes time, which may affect morbidity and mortality., Methods: This was a retrospective review of one case., Results: A 56-year-old woman presented with bilateral amelanotic choroidal masses suspicious for metastases of unknown origin. Plasma circulating tumor DNA revealed EGFR , PTEN , and SMAD4 , a profile consistent with non-small-cell lung cancer. Subsequent radiographic imaging and scapular biopsy revealed lung adenocarcinoma and genetic profile concordant with the liquid biopsy. The patient was started on EGFR inhibitor, osimertinib, with measurable systemic and ocular response., Conclusion: Plasma circulating tumor DNA revealed the genetic profile of the primary malignancy underlying choroidal metastases of unknown origin, aiding in the prompt diagnosis and detecting the driver mutation that guided management with targeted therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: Optimal local treatment for pulmonary oligometastases from colorectal cancer (CRC) remains unclear. We aimed to compare the long-term survival outcomes between surgery and stereotactic body radiation therapy (SBRT) as the initial local treatment for CRC pulmonary oligometastases., Materials and Methods: We retrospectively reviewed 335 consecutive patients who initially underwent surgery or SBRT for CRC pulmonary metastases from 2011 to 2022, and 251 patients (173 surgery and 78 SBRT) were ultimately included. Freedom from intrathoracic progression (FFIP), progression-free survival (PFS), and overall survival (OS) were compared using stabilized inverse probability of treatment weighting (sIPTW) analysis. In addition, patterns of intrathoracic progression and subsequent treatment were analyzed., Results: Median follow-up was 61.6 months for surgery and 54.4 months for SBRT. After sIPTW adjustment, significant differences emerged in both FFIP and PFS between surgery and SBRT (FFIP: hazard ratio [HR] = 0.50, 95% confidence interval [CI], 0.31-0.79; PFS: HR = 0.56, 95% CI, 0.36-0.87). The 3- and 5-year FFIP rates were 58.6% and 54.8%, respectively, after surgery, and 34.6% and 31.3%, respectively, after SBRT (P = .006). The 3- and 5-year PFS rates were 49.4% and 45.2%, respectively, after surgery, and 28.8% and 26.1%, respectively, after SBRT (P = .010). However, OS was not significantly affected by treatment approach (HR = 0.93, 95% CI, 0.49-1.76). The 3- and 5-year OS rates were 85.9% and 73.1%, respectively, after surgery, and 78.9% and 68.7%, respectively, after SBRT (P = .849). Recurrence at the treated site was more prevalent after SBRT than after surgery (33.3% vs 16.9%), whereas new intrathoracic tumors occurred more frequently after surgery than after SBRT (71.8% vs 43.1%). Both groups chose radiation therapy as the primary local salvage treatment., Conclusions: Notwithstanding the significant differences in FFIP and PFS between surgery and SBRT, the long-term survival of patients with CRC pulmonary oligometastases did not depend on the initial choice of the local treatment approach., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Osteosarcoma (OS) cells commonly suffer from hypoxia and dedifferentiation, resulting in poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated cellular signaling., Methods: We performed sphere formation assays and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers. RNAi assay was used to explore the relationship between hypoxia inducible factor 1 subunit alpha (HIF1A) and platelet derived growth factor receptor beta (PDGFRB). We obtained PDGFRB knockdown and overexpression cells through lentiviral infection experiments and detected the expression of PDGFRB, p-PDGFRB, focal adhesion kinase (FAK), p-FAK, phosphorylated myosin light chain 2 (p-MLC2), and ras homolog family member A (RhoA) in each group. The effects of PDGFRB on cytoskeleton rearrangement and cell adhesion were explored by immunocytochemistry. Wound-healing experiments, transwell assays, and animal trials were employed to investigate the effect of PDGFRB on OS cell metastasis both in vitro and in vivo., Results: Dedifferentiated OS cells were found to exhibit high expression of HIF1A and PDGFRB, and HIF1A upregulated PDGFRB, subsequently activated RhoA, and increased the phosphorylation of MLC2. PDGFRB also enhanced the phosphorylation of FAK. The OS cell morphology and vinculin distribution were altered by PDGFRB. PDGFRB promoted cell dedifferentiation and had a significant impact on the migration and invasion abilities of OS cells in vitro. In addition, PDGFRB increased pulmonary metastasis of OS cells in vivo., Conclusion: Our results demonstrated that HIF1A up-regulated PDGFRB under hypoxic conditions, and PDGFRB regulated the actin cytoskeleton, a process likely linked to the activation of RhoA and the phosphorylation of, thereby promoting OS dedifferentiation and pulmonary metastasis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Chunlin Zhang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Metastasectomy is a useful adjunct in the management of metastatic cancer. Widespread adoption of novel targeted and immunotherapies has improved the survival profiles of multiple malignancies, which has potentially altered the role of metastasectomy. This study aimed to characterize trends in metastasectomy across five primary cancers eligible for these therapies., Methods: The National Inpatient Sample was used to identify patients who underwent metastasectomy in the United States (2016-2021). Patients with procedure codes for resection of the lung, liver, adrenal gland, brain, or small bowel and concurrent diagnosis codes for secondary malignant neoplasm of that site were included. Subjects were subcategorized by primary malignancy: colorectal cancer, lung cancer, breast cancer, melanoma, or renal cancer. Sample weights were used to produce national estimates, which were incidence adjusted by primary malignancy. Trends in utilization were calculated with average annual percent change (AAPC) and linear regression coefficients., Results: Colorectal cancer was the most frequent indication for metastasectomy (n = 57,644 cases), followed by lung cancer (n = 55,090 cases), breast cancer (n = 12,616 cases), renal cancer (n = 8427 cases), and melanoma (n = 5658 cases). Utilization of metastasectomy increased over the study period for breast cancer (AAPC, +10.6%; p = .013) and melanoma (AAPC, +8.3%; p = .040) but did not change for lung cancer (AAPC, -1.6%; p = .26), colorectal cancer (AAPC, +0.3%; p = .83), or renal cancer (AAPC, +2.3%; p = .36)., Conclusions: Between 2016 and 2021, utilization of metastasectomy increased significantly for melanoma and breast cancer. The role of metastasectomy will likely continue to develop as new treatment protocols improve survival profiles for patients with metastatic disease., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Monocytes and monocyte-derived macrophages facilitate cancer progression and metastasis. Inflammatory monocytes expressing CCR2 are actively recruited to metastatic lungs, where they promote tumor cell extravasation, metastatic outgrowth, and an immunosuppressive environment. The role of CCR1 in this process has remained unclear. We used Ccr1- and Ccr2-deficient mice and two different tumor cells lines, MC38 and LLC1 with and without Ccl2-deficiency in vitro and in vivo. The recruitment of both Ccr1- and Ccr2-deficient monocytes towards the Ccl2 chemokine was significantly impaired, while no substantial recruitment was observed towards Ccl5 in vitro. MC38 and LLC1 Ccl2-deficient tumor cells showed reduced lung metastasis in both Ccr1- and Ccr2-deficient mice when compared to wild-type mice. We detected reduced numbers of macrophages and myeloid cells in both chemokine receptor-deficient mice. Lung metastasis in both Ccr1- and Ccr2-deficient mice could be rescued to the same levels as in wild-type mice by an adoptive transfer of Ccr2-deficient but not Ccr1-deficient monocytic cells. Accumulation of Ccr1-deficient monocytes in the lungs was severely impaired upon intravenous monocyte injection, indicating the importance of this axis in cell recruitment. Moreover, the efficient recruitment of adoptive transferred Ccr2-deficient monocytes to the lungs and the restoration of lung metastasis suggests an involvement of an additional, Ccr2-independent chemokine pathway. This data defines the non-redundant functions of the Ccr1- and Ccr2-chemokine axes in monocyte recruitment and macrophage presence during lung metastasis. While Ccr2 is essential for the release of monocytes from the bone marrow, Ccr1 is primarily responsible for monocyte presence at metastatic sites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Cancer presents a significant public health concern, particularly in the context of metastatic disease. Surgical removal of primary tumors, while essential, can inadvertently heighten the risk of metastasis. Thus, there is a critical need for innovative neoadjuvant therapies capable of curtailing metastatic progression before or immediately following tumor resection. Addressing this imperative, the papaya mosaic virus nanoparticle (PapMV) has demonstrated potent immunostimulatory capabilities against both viruses and tumors, effectively hindering their proliferation. Our study reveals that PapMV exerts a protective effect against lung metastasis when administered systemically prior to tumor implantation or during the early stages of metastasis in various mouse models of cancer. This anti-tumor effect is initiated by the recruitment of myeloid cells in the lungs. These cells adopt a pro-inflammatory profile, secreting cytokines such as IFN-α, thus fostering a tumor microenvironment inhospitable to tumor progression. Crucially, this protective mechanism hinges on the presence of macrophages before treatment. TLR7 and IFN-I signaling pathways also play pivotal roles in this process. Furthermore, our findings demonstrate that PapMV triggers the activation of the bone marrow emergency response, which accounts for the influx of myeloid cells into the lungs. This study unveils a novel aspect of PapMV's functionality. By bolstering the immune system, PapMV confers robust protection against metastasis at an early stage of disease progression. This discovery holds promise for therapeutic intervention, particularly as a preemptive measure prior to or just after surgical intervention.

Background: Interleukin-2 (IL-2) is a well-known cytokine that plays a crucial role in stimulating immune cells, including natural killer (NK) cells and cytotoxic T cells. It has been studied as an immunotherapy for a variety of diseases, including cancer. However, due to its short serum half-life, high doses of IL-2 are required which can result in systemic toxicities like capillary leak syndrome., Objective: To demonstrate the enhanced antitumor efficacy of Albumin Binding Domain-conjugated IL-2 (ABD-IL-2) at a lower dose compared to IL-2., Methods: IL-2 and ABD-IL-2 were purified using Ni-NTA resin with a histidine sequence added to their C-terminal region for purification purpose. Peripheral blood lymphocytes were stimulated with IL-2 and ABD-IL-2 to assess their function. 4T1 cells were injected into BALB/c mice to establish a breast cancer model with metastasis evaluated in the lungs., Results: Both recombinant proteins significantly stimulated T lymphocyte proliferation compared to the negative control (P=0.000, P=0.001). Administration of both proteins reduced the size of isolated tumors in the breast cancer mouse model. The control group had more nodules and larger lung metastatic centers (P=0.000). Metastasis to secondary lymphoid organs occurred only in the control group., Conclusion: By using ABD-IL-2 at a one-third concentration compared to IL-2, we aimed to reduce administration toxicity associated with high doses of IL-2 in immunotherapy. This approach shows potential for improving IL-2-based treatments while minimizing adverse effects.

Background: Epithelioid hemangioendothelioma (EHE) is an uncommon vascular malignancy characterized by an unpredictable clinical course and a high potential for recurrence and metastasis. The lack of standard treatment guidelines, coupled with the tumor's inconsistent response to available treatments, complicates the management of EHE and leads to widely varying patient prognoses., Case Presentation: We report two cases of EHE with distinct presentations reflecting the site of involvement. The first case involved a patient with pulmonary EHE who initially benefited from complete surgical resection of the tumor after chemotherapy. However, the patient experienced two episodes of metastatic recurrence, resistant to further surgical and chemotherapeutic interventions, ultimately leading to the patient's death forty-two months after the diagnosis. The second case presented with a mediastinal EHE involving the para-esophageal area. Partial tumor resection was achieved but postoperative imaging revealed extensive metastasis and pleural effusion. Despite additional treatments, the disease progressed rapidly, and the patient passed away fourteen months following the initial diagnosis., Conclusions: The optimal therapeutic approach for EHE remains controversial due to its unpredictable treatment response, particularly in recurrent or metastatic cases. Therapeutic investigations are needed to establish evidence-based guidelines that can address treatment challenges and ensure the best possible outcome for each patient., Competing Interests: Declarations. Ethics approval and consent to participate: The present study was approved by the medical Ethics committee of the University. Written informed consent was obtained from the patients regarding reporting of their data and images. Consent for publication: Written informed consent was obtained from the patients regarding the publication of this case report. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Immune-based combinations have significantly improved the treatment of metastatic renal cell carcinoma (mRCC); however, immunotherapy has reported varying degrees of efficacy across different metastatic sites, with liver and bone metastases traditionally considered more challenging to treat. In MOUSEION-08 study, we aimed to investigate the association between lung, liver, and bone metastases and clinical outcomes such as Overall Survival (OS) and Progression- Free Survival (PFS) in mRCC patients receiving immune-based combinations. The present systematic review and study-level meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). PFS and OS were measured as Hazard Ratios (HRs) and 95% confidence intervals (CIs). The protocol was registered with PROSPERO, Registration number: CRD42024581488. Our search resulted in the identification of 2364 potentially relevant reports, which were subsequently restricted to three. The pooled HRs for OS and PFS in patients with lung metastases receiving immune-based combinations versus sunitinib were 0.61 (95% CI, 0.51-0.72) and 0.47 (95% CI, 0.38-0.59), respectively. In patients with liver metastases, the pooled HRs for OS and PFS were 0.56 (95% CI, 0.42-0.75) and 0.48 (95% CI, 0.34-0.67), while the pooled HRs for OS and PFS in patients with bone metastases were 0.64 (95% CI, 0.49-0.84) and 0.36 (95% CI, 0.27-0.49), respectively. According to our findings, the analyses reported similar HRs for OS and PFS, something that further underlines the role of immune-based combinations in this setting, regardless of metastatic sites, such as lung, liver, and bone metastases. Ongoing research and clinical trials are destined to refine and improve immunotherapeutic strategies for mRCC, aiming to enhance efficacy across all metastatic sites and to define predictive biomarkers., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Patient-derived tumor organoids (PDTOs) models have been widely used to investigate the response of primary cancer tissues to anti-cancer agents. Nonetheless, only few case study tried to establish PDTOs and test treatment response based on bone metastasis (BoM) tissues. Fresh BoM tissues were obtained from lung cancer (LC) patients who underwent spinal metastatic tumor surgery for PDTOs culture. Morphology of LC-BoM-PDTOs were characterized during the process: they were high-efficient in self-assembly and regeneration, forming mature 3D-multicellular structures in 2-3 weeks. To be more specific, organoids of BoM derived from patients with EGFR mutation tended to be follicular conglomeration and resembled "a bunch of grapes", while organoids of BoM derived from patients without driver gene mutation were featured with full sphere and "a ripe sunflower". PDTOs of BoM retained good consistencies of HE morphology and immunohistochemical markers expression with their parental BoM tissues. Down-regulation of receptor activator of nuclear factor kappa-B ligand (RANKL) expression in LC-BoM-PDTOs after in vitro DMAb intervention was associated with earlier clinical ossification efficacy of DMAb on BoM (median time: 5 vs. 8 months, P = 0.049). Accordingly, BoM-PDTOs can be expected to be a preferred model for predicting treatment response of bone metastatic tumors, considering its high-efficient expansion and good biological consistency with parental bone tumor tissues., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval:  Institutional approval was obtained. Consent to participate: Patients signed informed consent for specimen collection before surgery Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Small cell lung carcinoma metastatic to the stomach, whether synchronous or metachronous, is a rare phenomenon accounting for < 0.5% of lung cancers. Hence it can be overlooked by clinicians resulting in delayed diagnosis. This manuscript comments on Yang et al 's article which reported 3 such cases. The main diagnostic features are based on routine morphology comprised of small cells with hyperchromatic nuclei, scant cytoplasm, brisk mitoses and necrosis. This can be supplemented by immunohistochemistry demonstrating positivity for cytokeratin, thyroid transcription factor-1 and neuroendocrine markers as well as a high Ki-67 labelling index. Imaging modalities such as positron emission tomography/contrast computed tomography help to confirm lung origin and rule out the possibility of extra-pulmonary small cell carcinoma. The predominant mechanism of spread is most likely hematogeneous. Prognosis is generally poor since this represents stage 4 disease but survival can be improved by chemo/radiotherapy and palliative surgery in select cases. Though outcomes have not changed much in the last several decades, the recent Food and Drug Administration approval of immune checkpoint inhibitors was a significant milestone as was the delineation of small cell lung carcinoma molecular subtypes. Liquid biopsies are increasingly being used for biomarker studies in clinical trials to assess treatment response and prognosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Renal abscesses require prompt diagnosis and appropriate intervention, as they can be life-threatening. However, diagnosis based solely on clinical findings is often challenging. We present the case of a 69-year-old woman with left renal masses on follow-up computed tomography (CT) after surgery for pT2aN0M0 lung carcinosarcoma. The masses were localized only in the left kidney without suspected metastatic lesions at other sites. The patient was referred to our department for further evaluation and treatment under a diagnosis of suspected metastatic lung carcinosarcoma of the left kidney. On enhanced CT, the left renal masses, the largest of which had a diameter of 40×36 mm had thick irregular walls gradually enhanced by the contrast media and an internal low-attenuation area. The masses showed heterogeneous signal intensity with a pseudocapsule on T2-weighted magnetic resonance imaging. Clinical symptoms such as fever or costovertebral angle tenderness were absent, and blood and urine tests were not sufficiently inflammatory to suggest a renal abscess. Histopathological findings on CT-guided renal biopsy revealed only inflammatory tissue and no tumor cells. However, because lung carcinosarcoma metastatic nodules could not be ruled out, laparoscopic left nephrectomy was performed for a definitive diagnosis and curative intent. The pathological diagnosis was renal abscess without malignant lesions. Here, we present a case of renal abscess mimicking metastatic lesions in a patient with lung carcinosarcoma. Accurately differentiating renal abscesses from metastatic renal tumors before treatment is often difficult. Renal abscess diagnosis should be considered through a comprehensive evaluation of the clinical findings of individual cases.

Breast cancer is one of the most common tumors in the world and metastasis is the major cause of tumor-related death. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and often associated with cancer metastasis. Nevertheless, the mechanism by which TAMs regulate breast cancer metastasis remain unclear. In this study, we found that transglutaminase 2 (TGM2) could serve as a crucial target in the modulation of TAMs-induced epithelial-mesenchymal transition (EMT) and invasion of breast cancer cells. Further analysis revealed that IL-6 secreted from TAMs, which was capable of inducing TGM2 expression through the activation of the JAK/STAT3 signaling pathway. Subsequent luciferase reporter assays demonstrated that STAT3 binds to the TGM2 promoter region, thereby transcriptionally enhancing TGM2 expression. In conclusion, our current research has identified the IL-6/STAT3/TGM2 axis as a pivotal regulator in breast tumorigenesis caused by TAMs, presenting a novel target for the treatment of breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Copper promotes tumor growth and metastasis through a variety of mechanisms, most notably as a cofactor within the lysyl oxidase (LOX) family of secreted cuproenzymes. Members of this family, which include LOX and LOX-like enzymes LOXL1-4, catalyze the copper-dependent crosslinking of collagens and elastin within the extracellular matrix (ECM). Elevated LOX expression is associated with higher incidence and worse prognosis in multiple cancers, including colorectal, breast, pancreatic, and head and neck. In this study, we demonstrated that elevated LOX expression correlates with decreased overall survival and shorter median time to first progression in patients with lung cancer. Previous studies have demonstrated that LOX secreted from tumors is critical for pre-metastatic niche formation by promoting ECM remodeling and the recruitment of immune cells and endothelial precursors. Here, we demonstrated that ablation of the LOX gene in Lewis lung carcinoma (LLC) cells diminishes tumor growth and metastasis compared to wild-type LLC cells in a syngeneic mouse model. Although the role of tumor-derived LOX in tumor formation and metastasis is well established, little is known regarding the possible contribution of LOX produced by the parenchymal tissue of metastatic organs. Thus, this report describes our findings that host-derived LOX produced by the lung contributes to the pulmonary metastasis of LLC cells in mice. The suppression of pulmonary lysyl oxidase expression reduces the metastatic potential of Lewis Lung Carcinoma cells in mice, revealing a previously unknown influence of LOX expression in the parenchymal tissue of metastatic target organs on the seeding of tumor cells., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)