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Background: Cancer ravages all aspects of a patient's life. In recent decades, there has been a substantial paradigm shift in the treatment of cancer with an emphasis on quality of life and patient comfort. Patients are treated holistically, a complex task given how multifaceted cancers are. Voice, a subtle indicator of patients' well-being is affected commonly by malignancies. One of the various ways by which voice is disturbed by non-laryngeal cancers is through metastasis to the larynx and adjacent areas. Metastasis to the larynx is rare but well-documented. If not diagnosed in a timely fashion, it can have devastating consequences on patients from life-threatening airway obstruction to progressive dysphonia that erodes their quality of life. Metastatic lesions of the larynx usually appear submucosal with intact overlying mucosa and are located most commonly in the supraglottis. Deep biopsies usually are needed for diagnosis, and management may entail endoscopic resection or other treatments., Objectives: This paper reviews the literature to identify typical features of laryngeal metastatic lesions of the ten cancers that are among the most common worldwide, ie, skin, renal, breast, colorectal, lung, prostate, thyroid and liver. By summarizing their most prevalent locations in the larynx, type and appearance, the authors hope to aid physicians in their diagnostic process, particularly in cases in which laryngeal involvement is the first presenting sign of a malignancy., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Radiotherapy is considered an alternative treatment for unresectable or pharmacologically resistant desmoid-type fibromatosis. While it results in relatively good local control, the risk of secondary malignancy remains a concern., Case: We present a case of secondary osteosarcoma after carbon-ion radiation therapy (CIRT). A 31-year-old male patient presented with left thigh pain. The tumor was located between the left gluteus maximus and gluteus medius and extended to the vastus lateralis and biceps femoris. It was diagnosed as desmoid-type fibromatosis after needle biopsy. The patient was treated with several medications, including a cyclooxygenase 2 inhibitor and tamoxifen; however, his left thigh pain did not improve. He was treated with CIRT 1 year after diagnosis (67.2 Gy [relative biological effectiveness] 16fr/4wks). He developed osteosarcoma of the left femur 8 years later. He underwent chemotherapy and tumor excision with disarticulation of the left hip. Pulmonary metastasis was detected 6 and 17 months after the definitive surgery and excised using metastasectomy. However, he died due to the recurrence of multiple pulmonary metastases 29 months after the definitive surgery., Conclusions: In this case, we believe that the low radiation dose to the femur may have caused secondary malignancy., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Astrocytomas are relatively common primary brain tumours of humans and companion animals. In dogs, they represent approximately 17-28% of primary central nervous system tumours. However, extracranial metastasis is extremely rare. This case report describes a grade IV astrocytoma (glioblastoma) in the cerebrum of a young Cane Corso dog with pulmonary metastases. The diagnosis was obtained via histopathological morphology and immunophenotyping, which showed strong positivity for glial fibrillary acidic protein, vimentin and connexin-43. The glioblastoma in this Cane Corso had epithelioid morphology with histological features of malignancy including high mitotic count, microvascular proliferation, serpentine necrosis and subventricular zone involvement. Epithelioid glioblastoma is a rare subtype that has only relatively recently been formally acknowledged in human medicine and it can also pose a diagnostic challenge in veterinary medicine., Competing Interests: Declaration of competing interests The authors declared no conflicts of interest in relation to the research, authorship or publication of this article. This study was carried out for the small animal module in fulfilment of the MSc in Veterinary Pathology at the University of Liverpool., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The aim of this study was to find the most appropriate variables to input into machine learning algorithms to identify those patients with primary lung malignancy with high risk for metastasis to the bone., Patient Inclusion: Patients with either histological or radiological diagnoses of lung cancer were included in this study., Results: The patient cohort comprised 1864 patients diagnosed from 2016 to 2021. A total of 25 variables were considered as potential risk factors. These variables have been identified in previous studies as independent risk factors for bone metastasis. Treatment methods for lung cancer were taken into account during model development. The outcome variable was binary, (presence or absence of bone metastasis) with follow-up until death or 12-month survival, whichever is the sooner. Results showed that American Joint Committee on Cancer staging, the use of EGFR inhibitor, age, T-staging, and lymphovascular invasion were the five input features contributing the most to the model algorithm. High AJCC staging (OR 1.98; p < 0.05), the use of EGFR inhibitor (OR 6.14; p < 0.05), high T-staging (OR 1.47; p < 0.05), and the presence of lymphovascular invasion (OR 4.92; p < 0.05) increase predicted risk of bone metastasis. Conversely, older age reduces predicted bone metastasis risk (OR 0.98; p < 0.05)., Conclusion: The machine learning model developed in this study can be easily incorporated into the hospital's Clinical Management System so that input variables can be immediately utilized to give an accurate prediction of bone metastatic risk, therefore informing clinicians on the best treatment strategy for that individual patient., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

A 26-year-old male presented to a hospital with complaints of hemoptysis and right scrotal swelling. Computed tomography (CT) revealed right testicular swelling, multiple lung metastases, and small intestinal wall thickening. The patient's β-human chorionic gonadotropin, alpha-fetoprotein, lactate dehydrogenase, and hemoglobin levels were 103.3 ng/ml, 20.8 ng/ml, 300 U/l, and 11.3 g/dl, respectively. He underwent high orchidectomy after being diagnosed with a testicular tumor and multiple lung metastases. Histopathological examination revealed a mixed germ cell tumor (60% choriocarcinoma, 20% seminoma, 10% embryonal carcinoma, 10% mature teratoma, and 1% yolk sac tumor). As the patient exhibited active gastrointestinal hemorrhage requiring frequent blood transfusions, gastrointestinal endoscopy was performed to investigate its cause. When upper and lower gastrointestinal endoscopies revealed no bleeding, the patient was referred to our hospital for further examination and treatment. A small bowel endoscopy revealed a hemorrhagic jejunal mass. Because endoscopic hemostasis was challenging, we partially resected the small intestine. Pathological findings in the resected lesion were consistent with small intestinal metastasis of the testicular tumor. The tumor markers turned negative after four cycles of BEP and four cycles of TIP chemotherapy. He then underwent resection of the remaining lung tumor, and no residual tumor or recurrence was detected one year later.

mRNA-based applications have achieved remarkable success in the development of next-generation vaccines and the treatment of diverse liver diseases. Overcoming the challenge of delivering mRNA to extrahepatic tissues, especially specific cells within tissues, is crucial for precision therapy. In this study, a platform is developed for selective mRNA delivery to desired cells within tissues by combining lipid nanoparticle (LNP)-based targeted delivery with mRNA sequence-controlled expression. Through systematic optimization, a three-component LNP platform is developed, enabling targeted mRNA delivery to the lung, liver, and spleen. The incorporation of unique microRNA target sites into the mRNA scaffold further enhances control over protein translation in specific cells within the target tissue. This combined strategy, named SELECT (Simplified LNP with Engineered mRNA for Cell-type Targeting), demonstrates its efficacy in distinguishing mRNA expression between tumor and normal cells based on intracellular microRNA abundance. SELECT encapsulating mRNA encoding a tumor-specific cytotoxic protein, human ELANE, exhibits selective mRNA delivery to tumor lesions and significant inhibition of tumor growth in a mouse model of melanoma lung metastasis. Overall, SELECT has great potential as a new precision tumor treatment approach and also offers promising prospects for other mRNA therapies targeting specific cell types., (© 2024 Wiley‐VCH GmbH.)

Ethnopharmacological Relevance: In China, Maimendong Decoction (MMDD) is a classic Chinese medicine prescription for treating lung diseases, such as cough, upper respiratory tract infection, bronchitis, asthma, pulmonary fibrosis and so on. However, the mechanism by which MMDD inhibits lung cancer metastasis remains unclear., Aim of the Study: This study seeks to examine the effect of MMDD on suppressing lung cancer metastasis and to uncover its mechanism through the regulation of tumor immunity., Materials and Methods: The impact of MMDD on lung cancer cell growth and metastasis was assessed via cell apoptosis, proliferation, and migration assays, alongside lung metastasis models in mice. Hematoxylin-eosin (H&E) staining, immunohistochemistry, and immunofluorescence were used to examine the tissue morphology of metastatic tumors, Ki-67 protein expression, and NK cell infiltration. The potential anti-lung cancer mechanism of MMDD was explored through network pharmacology. Immune cell levels and NK cell function in mouse peripheral blood were analyzed using flow cytometry. Additionally, co-culture and lactate dehydrogenase (LDH) assays were performed to assess NK cell cytotoxicity., Results: MMDD significantly reduced the number of metastatic tumors and the neoplastic burden in the lungs of mice. While MMDD did not affect the proliferation, apoptosis, or migration of lung cancer cells at 1 mg/ml concentration in vitro, it substantially increased NK cell proportion in peripheral blood and metastatic tumor tissues. Moreover, MMDD significantly boosted NK cell cytotoxicity and enhanced their killing effect on lung cancer cells. Importantly, depletion of NK cells abolished the survival-prolonging effect of MMDD in mice., Conclusion: This study demonstrates that MMDD restrains lung cancer cell metastasis primarily by increasing NK cell levels and enhancing their cytotoxic activity. These results offer experimental support for the use of MMDD in treating lung cancer metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Although there is a growing role for local therapy in patients with hepatocellular carcinoma (HCC) and pulmonary oligometastasis, it remains unclear whether metastatectomy or stereotactic body radiation therapy (SBRT) is the more effective treatment for these patients. We aimed to compare the oncologic outcomes of metastasectomy and SBRT for HCC with pulmonary oligometastasis., Methods and Materials: We retrospectively analyzed 209 patients with HCC with 322 metastatic lung lesions who underwent either metastasectomy (150 patients with 241 lesions) or SBRT (59 patients with 81 lesions) between January 2008 and December 2018. Propensity score-based inverse probability of treatment weighting was used to minimize potential bias between the 2 groups., Results: The median follow-up duration was 39.8 months (range, 2.3-166.9 months). The 2-year rate of freedom from local progression was 98.2% in the metastasectomy group and 97.0% in the SBRT group (P = .197). The 2-year rates of overt systemic progression-free survival (PFS) (51.0% vs 46.1%; P = .274), PFS (26.3% vs 9.1%; P = .074), and overall survival (OS, 74.0% vs 57.6%; P = .006) were higher in the metastasectomy group. After the probability of treatment weighting adjustment, the 2-year rates of overt systemic PFS (50.8% vs 52.7%; P = .396), PFS (23.0% vs 24.7%; P = .478), and OS (72.6% vs 83.0%, P = .428) were not significantly different between the 2 groups. In multivariate analysis, viable intrahepatic lesions and the number of prior liver-directed therapies were found to be significant prognostic factors for OS and PFS. The time interval between HCC diagnosis and the development of pulmonary metastases was also significantly associated with OS., Conclusions: Both metastasectomy and SBRT demonstrated excellent local control and comparable oncologic outcomes in patients with pulmonary oligometastasis from HCC. The treatment modality for these patients could be determined based on the individual patient's condition and intrahepatic disease status., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Treatment landscape in metastatic lung cancer has progressed quickly over the last decade, mainly due to immunotherapies and targeted therapies. This study aimed to describe change in epidemiological data of patients with metastatic lung cancer., Methods: A cohort of patients identified between 2013 and 2021 with lung cancer and a marker of metastases (ICD-10 code or reimbursement for Bevacizumab or Pemetrexed) was built from the French claims database. A trend analysis of the rate of newly-diagnosed metastatic patients and the proportion of deaths over the study period was performed using Joinpoint® software., Results: Between 2013 and 2021, 147,760 metastatic lung cancer patients were identified (men: 66.5%, median age: 66 years). A statistically significant decrease in the crude rate of newly-diagnosed metastatic patients was observed in men (-1.18% per year in average), whereas a statistically significant increase was described in women (+2.36% per year in average). A downward trend in the proportion of deaths was found for both gender (-4.37% and -5.07% per year on average, respectively)., Discussion: This study provides unpublished epidemiological data on metastatic lung cancer in France and confirms sex-differentiated trends in the rate of newly-diagnosed metastatic patients, already observed for all stages combined. A statistically significant decrease in the proportion of deaths among metastatic lung cancer patients is observed in both genders. These results underline the importance of ongoing investments in prevention and screening initiatives to reverse the incidence trends observed in women. Moreover, it highlights the criticality of therapeutic innovation in sustaining the increase in survival., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The lung is a highly vascularized tissue that often harbors metastases from various extrathoracic malignancies. Lung parenchyma consists of a complex network of alveolar epithelial cells and microvessels, structured within an architecture defined by basement membranes. Consequently, understanding the role of the extracellular matrix (ECM) in the growth of lung metastases is essential to uncover the biology of this pathology and developing targeted therapies. These basement membranes play a critical role in the progression of lung metastases, influencing multiple stages of the metastatic cascade, from the acquisition of an aggressive phenotype to intravasation, extravasation and colonization of secondary sites. This review examines the biological composition of basement membranes, focusing on their core components-collagens, fibronectin, and laminin-and their specific roles in cancer progression. Additionally, we discuss the function of integrins as primary mediators of cell adhesion and signaling between tumor cells, basement membranes and the extracellular matrix, as well as their implications for metastatic growth in the lung. We also explore vascular co-option (VCO) as a form of tumor growth resistance linked to basement membranes and tumor vasculature. Finally, the review covers current clinical therapies targeting tumor adhesion, extracellular matrix remodeling, and vascular development, aiming to improve the precision and effectiveness of treatments against lung metastases., Competing Interests: Declaration of interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate safety and effectiveness of microwave ablation (MWA) in the treatment of liver metastases (LMs) secondary to non-small cell lung cancer (NSCLC)., Materials and Methods: This retrospective study included patients with NSCLC who underwent MWA of LM from March 2015 to July 2022. Local tumor progression-free survival (LTPFS) and overall survival (OS) were estimated using competing risk analysis and the Kaplan-Meier method. Postprocedural adverse events were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0., Results: Twenty-three patients with 32 LMs were treated in 27 MWA sessions. The mean dimension of the largest index tumor was 1.96 cm (SD ± 0.75). Technical success was 100%. Technical effectiveness was achieved in 26 (81.3%) of 32 tumors. The median length of follow-up was 37.7 months (interquartile range, 20.5-54.5 months). The median LTPFS was 16.3 months (95% confidence interval [CI], 7.87-44.10 months). The median OS was 31.7 months (95% CI, 11.1-65.8 months). Ablation margin was a significant factor for LTPFS, with tumors ablated without a measurable margin being more likely to progress than those with measurable margins (subdistribution hazard ratios [HRs], 0.008-0.024; P < .001). Older age (HR, 1.18; 95% CI, 1.09-1.28; P < .001) and presence of synchronous lung metastases (HR, 14.73; 95% CI, 1.86-116.95; P = .011) were significant predictors of OS. Serious adverse events (CTCAE Grade ≥3) within 30 days occurred in 2 (7.4%) of 27 sessions, including pulmonary embolus and severe abdominal pain., Conclusions: Percutaneous MWA was a safe treatment for NSCLC LM, with longer survival noted in younger patients and those without synchronous lung tumors., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Brain metastasis stands as a leading contributor to mortality in lung cancer patients, yet the intricate mechanism underlying this phenomenon remains elusive. This underscores the need for robust preclinical models and effective treatment strategies. Emerging as viable in vitro models that closely replicate actual tumors, three-dimensional culture systems, particularly organoids derived from non-malignant cells or cancer organoids, have emerged as promising avenues. This review delves into the forefronts of fundamental research and clinical applications focused on lung cancer brain metastasis-derived organoids, highlighting current challenges and delineating prospects. These studies offer tremendous potential for clinical application despite being in nascent status., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, author-ship, and publication of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Photodynamic Therapy (PDT) is a promising paradigm for treating cancer, especially superficial cancers, including skin and oral cancers. However, the effectiveness of PDT is hindered by the hydrophobicity of photosensitizers. Here, chlorin e6 (Ce6), a hydrophobic photosensitizer, was loaded into pluronic F127 micelles to enhance solubility and improve tumor-specific targeting efficiency. The resulting Ce6@F127 Ms demonstrated a significant increase in solubility and singlet oxygen generation (SOG) efficiency in aqueous media compared to free Ce6. The confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed the enhanced internalization rate of Ce6@F127 Ms in murine melanoma cell lines (B16F10) and human oral carcinoma cell lines (FaDu). Upon laser irradiation (666 nm), the cellular phototoxicity of Ce6@F127 Ms against B16F10 and FaDu was approximately three times higher than the free Ce6 treatment. The in vivo therapeutic investigations conducted on a murine model of skin cancer demonstrated the ability of Ce6@F127 Ms, when combined with laser treatment, to penetrate solid tumors effectively, which resulted in a significant reduction in tumor volume compared to free Ce6. Further, the Ce6@F127 Ms demonstrated upregulation of TUNEL-positive cells, downregulation of proliferation markers in tumor tissues, and prevention of lung metastasis with insignificant levels of proliferating cells and collagenase, as validated through immunohistochemistry. Subsequent analysis of serum and blood components affirmed the safety and efficacy of Ce6@F127 Ms in mice. Consequently, the developed Ce6@F127 Ms exhibits significant potential for concurrently treating solid tumors and preventing metastasis. The photodynamic formulation holds great clinical translation potential for treating superficial tumors., Competing Interests: Declarations. Ethics approval and consent to participate: In vivo experiments adhered to CPCSEA guidelines (BITS-Hyd/IAEC/2023/36) approved by IAEC, Department of Pharmacy, BITS Pilani, Hyderabad. Consent for publication: The authors declare that all authors have been actively involved in the work leading to this paper, and all take responsibility for the published work. Competing interests: The authors declare no competing interests., (© 2024. Controlled Release Society.)

Background/objectives: Alnustone (Aln) is an effective compound of Alpinia katsumadae Hayata. Aln possesses various pharmacological activities such as antibacterial, anti-inflammatory, and anti-cancer effects. However, the inhibitory effect of Aln on colorectal cancer (CRC) has not yet been identified. Thus, research was conducted to clarify whether Aln can suppress the proliferative and metastatic ability of CRC cells., Methods: A cell viability assay was performed to confirm the decrease in CRC cell viability following Aln treatment. Flow cytometry was carried out to evaluate the effects of Aln on cell cycle arrest, autophagy, and apoptosis in CRC cells. In addition, a lung metastasis animal model was used to check the inhibitory effect of Aln on the metastasis of CRC cells., Results: Aln remarkably diminished the viability and colony-forming ability of several CRC cell lines. In addition, Aln led to a halt at the G0/G1 phase through downregulating cyclin D1-CDK4 in CRC cells. The upregulation of LC3B and p62 expression by Aln triggered autophagy of CRC cells. Moreover, Aln promoted mitochondrial depolarization, resulting in apoptosis of CRC cells. Oral administration of Aln significantly restrained the metastasized lung tumor nodules., Conclusions: This study demonstrated that Aln can suppress the survival and lung metastasis of CRC cells by promoting cell cycle arrest, autophagy, and apoptosis.

Melittin has previously been found to have a positive effect on colorectal cancer (CRC) treatment, one of the most difficult-to-treat malignancies, but the mechanism by which this effect occurs remains unclear. We evaluated melittin's pro-apoptotic and anti-metastatic effects on CRC in vitro and in vivo. The results showed that melittin-induced mitochondrial ROS bursts decreased ΔΨm, inhibited Bcl-2 expression, and increased Bax expression in both cells and tumor tissues. This led to increased mitochondrial membrane permeability and the release of pro-apoptotic factors, particularly the high expression of Cytochrome C, initiating the apoptosis program. Additionally, through wound-healing and transwell assays, melittin inhibited the migration and invasion of CRC cells. In vivo, the anti-metastatic effect of melittin was also verified in a lung metastasis mouse model. Western blotting and immunohistochemistry analysis indicated that melittin suppressed the expression of MMPs and regulated the expression of crucial EMT markers and related transcription factors, thereby inhibiting EMT. Furthermore, the melittin disrupts neovascularization, ultimately inhibiting the metastasis of CRC. In conclusion, melittin exerts anti-CRC effects by promoting apoptosis and inhibiting metastasis, providing a theoretical basis for further research on melittin as a targeted therapeutic agent for CRC.

Ground-glass nodules (GGNs) are generally considered an early stage of lung cancer. The imaging characteristics and curative efficacy of multiple GGNs as metastases remain unclear. Microsatellite instability-high (MSI-H) is a biomarker for immunotherapy. The therapeutic effect and prognosis for patients with MSI-H and Epidermal Growth Factor Receptor (EGFR)-sensitive mutation stays uncertain. Here, we report a case of a lung adenocarcinoma patient presenting with ground-glass metastases, MSI-H, and EGFR-sensitive mutation and provide clinical data on the efficacy and prognosis. We describe the predictive significance of carcinoembryonic antigen (CEA) for disease progression when there is inconsistency between treatment effectiveness and CEA changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He and Li.)

Rationale: Ovarian carcinosarcoma (OCS) is a rare malignant tumor prone to distant metastasis. Primary manifestations include pelvic and/or abdominal pain, bloating, and compression. Nevertheless, it is uncommon for OCS to present primarily with persistent fever. This is the first reported case of OCS with lung metastasis characterized by persistent fever., Patient Concerns: A 61-year-old female patient complaining of abdominal pain and fever was admitted to our hospital. Computed tomography showed an irregular, slightly low-density mass on the left side of the uterus and multiple solid nodules in both lungs., Diagnoses: She underwent cytoreductive surgery for pathologically confirmed stage IVB OCS., Interventions: She was administered chemotherapy after cytoreductive surgery. Given the patient's history of persistent fever and progressively enlarged pulmonary nodules, a pulmonary abscess was considered as a possible diagnosis. Following antibiotic therapy, the patient's high body temperature did not decrease; however, following nonsteroidal anti-inflammatory drug therapy, it quickly decreased. These symptoms were eventually considered the consequence of neoplastic fever caused by lung metastases., Outcomes: Owing to the rapid progression of the disease, the patient ultimately died., Lessons: This study suggests that, for patients with pelvic and/or abdominal pain, bloating, and pelvic masses, especially those with suspicious lesions in other organs accompanied by fever of unknown origin, a diagnosis of cancer or sarcoma with metastasis should be considered after ruling out infectious fever., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Progressive metastasis is the primary cause of cancer-related deaths. It has been recognized that many cancers are characterized by long periods of stability followed by subsequent progression. Genes termed metastasis progression suppressors (MPS) are functional gatekeepers of this process, and their loss leads to late-stage progression. Previously, we identified regulator of calcineurin 1, isoform 4 (RCAN1.4) as a functional MPS for several cancers, including thyroid cancer, a tumor type prone to metastatic dormancy. RCAN1.4 knockdown increases expression of the cancer-promoting transcription factor NFE2-like bZIP transcription factor (NFE2L3), and through this mechanism increases cancer cell proliferation and invasion in in vitro and in vivo and promotes metastatic potential to lungs in tail vein models. However, the mechanisms by which RCAN 1.4 regulates specific metastatic steps is incompletely characterized. Studies of the metastatic cascade are limited in mouse systems due to high cost and long duration. Here, we have shown the creation of a thyroid-to-lung metastasis-on-a-chip (MOC) model to address these limitations, allowing invasion analysis and quantification on a single cell level. We then deployed the platform to investigate RCAN1.4 knockdown in fluorescently tagged hTh74 and FTC236 thyroid cancer cell lines. Cells were circulated through microfluidic channels, running parallel to lung hydrogel constructs allowing tumor cell-lung tissue interactions. Similar to studies in mouse models, RCAN1.4 knockdown increased NFE2L3 expression, globally increased invasion distance into lung constructs and had cell line and clonally dependent variations on bulk metastatic burden. In line with previous in vivo observations, RCAN1.4 knockdown had a greater impact on hTh74 metastatic propensity than FTC236. In summary, we have developed and validated a novel MOC system evaluate and quantify RCAN1.4-regulated thyroid cancer cell lung adherence and invasion. This system creates opportunities for more detailed and rapid mechanistic studies the metastatic cascade and creates opportunities for translational assay development., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Lung enteric-type adenocarcinoma (ETAC) is a rare subtype of non-small cell lung cancer (NSCLC), comprising approximately 0.6% of all primary lung adenocarcinomas. It is characterized by a tendency for early metastasis and a prognosis comparable to that of common lung adenocarcinoma. This case report described a patient with lung-ETAC who developed gastric metastasis. The patient underwent treatment with chemotherapy and a PD-1 inhibitor, resulting in disease remission with a progression-free survival (PFS) of 8 months. The follow-up time was 13 months. This case report was aimed to enhance understanding of the biological behavior of this rare tumor and provide insights into potential future treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Ma, Ma, Zhao, Fan and Xu.)

Metastasis and recurrence are the main challenges in cancer treatment. Among various therapeutic approaches, immunotherapy holds promise for preventing metastasis and recurrence. In this study, we evaluated the efficacy of treating primary cancer and blocking metastasis and recurrence with photo-immunotherapeutic nanoparticles, which were synthesized using two types of charged polysaccharides. Codium fragile polysaccharide (CFP), which exhibits immune-stimulating properties and carries a negative charge, was combined with positively charged chitosan to synthesize nanoparticles. Additionally, indocyanine green (ICG), a photosensitizer, was loaded inside these particles and was referred to as chitosan-CFP-ICG (CC-ICG). Murine colon cancer cells (CT-26) internalized CC-ICG, and subsequent 808-nanometer laser irradiation promoted apoptotic/necrotic cell death. Moreover, intratumoral injection of CC-ICG, with 808-nanometer laser irradiation eliminated CT-26 tumors in mice. Rechallenged lung metastases of CT-26 cancer were inhibited by dendritic cell activation-mediated cytotoxic T lymphocyte stimulation in mice cured by CC-ICG. These results demonstrated that CC-ICG is a natural tumor therapeutic with the potential to treat primary tumors and suppress metastasis and recurrence., (© 2024. The Author(s).)

As catabolic enzyme, CD73 dephosphorylates adenosine monophosphate (AMP) and can also regulate tumor cell proliferation and metastasis. To date, very few studies have explored the role of CD73 in mediating non-small cell lung cancer (NSCLC) metastasis, and the underlying transducing signal has not been elucidated. In the present study, we demonstrated that the CD73/Axl axis could regulate Smad3-induced epithelial-to-mesenchymal transition (EMT) to promote NSCLC metastasis. Mechanically, CD73 can be secreted via the Golgi apparatus transport pathway. Then secreted CD73 may activate AXl by directly bind with site R55 located in Axl extracellular domain independently of GAS6. In addition, we proved that CD73 can stabilize Axl expression via inhibiting CBLB expression. We also identified the distinct function of CD73 activity in adenocarcinoma and squamous cell carcinoma. Our findings indicated a role of CD73 in mediating NSCLC metastasis and propose it as a therapeutic target for NSCLC., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background and Objectives: Lung cancer is one of the prevailing malignancies worldwide. Surgical interventions hold an important position in the treatment framework for lung cancer. Pleural metastasis is often assumed to be a surgical contraindication, but not all instances of pleural metastasis can be accurately identified before surgery. The question of how to address pleural metastasis detected intraoperatively is still undecided., Methods: This retrospective study included 187 lung cancer patients who underwent surgery from 2005 to 2017 in whom pleural metastasis was discovered incidentally during the operation. Data on demographic, surgical, pathological, postoperative treatment, and survival information were collected for further analysis., Results: For patients with intraoperatively detected pleural metastasis, two independent protective prognostic factors were receiving primary tumor resection (compared to only receiving pleural nodule biopsy, HR = 0.079, p = 0.022) and receiving postoperative adjuvant chemotherapy (HR = 0.081, p < 0.001). Simultaneously, performing systematic lymph node dissection during primary tumor resection was found to be detrimental to long-term prognosis (HR = 2.375, p = 0.044). However, the resection of pleural metastatic lesions did not significantly impact patient prognosis., Conclusion: Our study supports the implementation of major tumor resection in patients with pleural metastasis detected intraoperatively but not lymph node dissection or the resection of pleural metastatic lesions. Postoperative chemotherapy is also necessary., (© 2024. The Author(s).)

Background: Choriocarcinoma is an aggressively invasive neoplasm, characterized by its rapid proliferation and propensity for metastasis to distant organs via hematogenous dissemination. Lungs (80%), vagina (30%), pelvis (20%), liver (10%), and brain (10%) are the most frequently metastasized organs. Renal metastases are very rare. The clinical manifestations of choriocarcinoma varies depending on the site of disease, making diagnosis challenging. In this report, we provide a clinical case of choriocarcinoma with metastases to the renal and pulmonary systems, displaying symptoms akin to those observed in ectopic pregnancy., Case Presentation: A 27-year-old female, G2P1, with a previous history of full-term pregnancy in 2018, presented to the hospital with the onset of vaginal bleeding and accompanying abdominal aches. Investigations uncovered a left adnexal mass with a human chorionic gonadotropin (hCG) level of 77,4 mIU/mL and a left pulmonary nodule measuring 31 mm x 21 mm. Laparoscopy was performed due to the high suspicion of an ectopic pregnancy. However, no visible villi were identified during the surgery, and postoperative blood hCG levels continued to rise. A diagnostic curettage also failed to reveal any villi, maintaining the suspicion of a persistent ectopic pregnancy. Following two ineffective courses of methotrexate therapy, the patient was referred to our facility. Prior to her referral, an ultrasound had indicated a mass in the right kidney. However, upon arrival at our hospital, subsequent ultrasonography failed to detect any renal masses. Despite two months of outpatient monitoring, there was a sudden and significant increase in her serum hCG levels. An emergency laparoscopy was performed, revealing no pregnancy-related lesion. After surgery, the patient's hCG levels dropped dramatically to less than one-tenth of the original amount. Multisite enhanced computed tomography(CT)revealed suspicious lesions in both the renal and pulmonary regions. Upon thorough multidisciplinary consultation, a diagnosis of choriocarcinoma was entertained. Consequently, the patient successfully underwent eight cycles of chemotherapy and has remained recurrence-free for the past year., Conclusions: This case underscores the potential for choriocarcinoma in women of reproductive age who exhibit radiological signs of renal masses. Early and accurate diagnosis, followed by prompt intervention, is essential to prevent needless surgery procedures., (© 2024. The Author(s).)

Nanocatalytic immunotherapy holds excellent potential for future cancer therapy due to its rapid activation of the immune system to attack tumor cells. However, a high level of N-glycosylation can protect tumor cells, compromising the anticancer immunity of nanocatalytic immunotherapy. Here, we show a 2-deoxyglucose (2-DG) and bismuth ferrite co-loaded gel (DBG) scaffold for enhanced cancer piezocatalytic immunotherapy. After the implantation in the tumor, DBG generates both reactive oxygen species (ROS) and piezoelectric signals when excited with ultrasound irradiation, significantly promoting the activation of anticancer immunity. Meanwhile, 2-DG released from ROS-sensitive DBG disrupts the N-glycans synthesis, further overcoming the immunosuppressive microenvironment of tumors. The synergy effects of ultrasound-triggered and glycosylation inhibition enhanced tumor piezocatalytic immunotherapy are demonstrated on four mouse cancer models. A "hot" tumor-immunity niche is produced to inhibit tumor progress and lung metastasis and elicit strong immune memory effects. This work provides a promising piezocatalytic immunotherapy for malignant solid tumors featuring both low immunogenicity and high levels of N-glycosylation., (© 2024. The Author(s).)

Approximately 50% of patients with surgically resected early-stage lung cancer develop distant metastasis. At present, there is no in vivo metastasis model to investigate the biology of human lung cancer metastases. Using well-characterized lung adenocarcinoma (LUAD) patient-derived organoids (PDOs), we establish an in vivo metastasis model that preserves the biologic features of human metastases. Results of whole-genome and RNA sequencing establish that our in vivo PDO metastasis model can be used to study clonality and tumor evolution and to identify biomarkers related to organotropism. Investigation of the response of KRAS G12C PDOs to sotorasib demonstrates that the model can examine the efficacy of treatments to suppress metastasis and identify mechanisms of drug resistance. Finally, our PDO model cocultured with autologous peripheral blood mononuclear cells can potentially be used to determine the optimal immune-priming strategy for individual patients with LUAD., Competing Interests: Declaration of interests G.R. has financial relationships with Scanlan, AstraZeneca, and Medtronic. S.S. is a member of the AstraZeneca Advisory Board. J.M.I. has stock ownership in LumaCyte and is a consultant/advisory board member for Roche Genentech. M.J.B. is a consultant for AstraZeneca, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. B.T.L. has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly; has received research grants (institutional) from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, and Lilly; has received academic travel support from Amgen, Jiangsu Hengrui Medicine, and MORE Health; and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. M.H.B. receives royalties from Globus Medical and DePuy Synthes. P.S.A. declares research funding from Atara Biotherapeutics; is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPACT Bio, Johnson & Johnson, Orion, and Outpace Bio; has patents, royalties, and intellectual property on mesothelin-targeted chimeric antigen receptor and other T cell therapies, which have been licensed to Atara Biotherapeutics; and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. MSK has licensed intellectual property related to mesothelin-targeted chimeric antigen receptors and T cell therapies to Atara Biotherapeutics and has associated financial interests. D.R.J. serves on a clinical trial steering committee for AstraZeneca and has research grant support from Merck., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Breast cancer is one of the most common malignancies that can lead to cutaneous metastasis. Dermatopathologists often play an important role in the diagnosis of breast cancer metastasis to the skin. Rarely, dermatopathologists render a histopathologic diagnosis of primary breast cancer. We discuss a 51-year-old man with metastatic breast adenocarcinoma who presented after admission to the intensive care unit in the setting of altered mental status and critical anemia. Examination revealed a 14cmx12cm ulcerated, fungating tumor occupying the left breast. A four mm punch biopsy from the mass showed cords of atypical cells infiltrating the mid-to-deep dermis positive for CK7, GATA3, ER and PR. CK20, P40, p63, and TTF1 stains were negative. HER2/NEU immunoperoxidase stain was negative. CA15-3 was elevated at 75U/ml. Taken together, he was diagnosed with primary left breast ductal adenocarcinoma, grade two with subsequent visceral metastases to the bones, lymph nodes, and lungs. Although male breast cancer makes up less than 1% of all breast cancers, its incidence has been increasing worldwide. Recognition of the unique clinical and histologic findings of primary breast carcinoma is important to avoid delay in the diagnosis and initiation of appropriate treatment.

Background: Brain metastasis (BM) from cervical cancer (CC) is extremely rare. The prognosis of BM is poor. To our knowledge, no satisfactory therapeutic and standard effective treatments have been established. Immune checkpoint inhibitors (ICIs) treatment is emerging as a promising treatment in recurrence and metastasis(B/M) cervical cancer in recent years., Case: We present a 50-year-old patient with CC who developed multiple metastasis (lung, brain and skin) 2 years after postoperative chemoradiotherapy. She received palliative therapy included chemotherapy, resection and stereotactic radiosurgery of BM with poor response. Then, the patient received second-line palliative monotherapy with a PD-1/CTLA-4 inhibitor(cadonilimab) and achieved clinical very good partial response (VGPR), a progression-free survival (PFS) of 14 months and overall survival of more than 18 months since BM., Conclusion: We report a case of cervical cancer with multiple metastasis receiving cadonilimab and achieved considerable response and survival benefit., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ni, Dong, Shou, Xu, Yin and Lou.)

Lung metastasis in breast cancer (BC) patients is one of the main reasons for their high mortality rate. The most prevalent BC small extracellular vesicles (sEVs receptor, integrin α6β4, has been found to interact with surfactant-associated protein (SFTPC) in lung epithelial cells, making BC more likely to metastasize to the lung. Tumor-associated neutrophils (TANs) play an essential role in BC lung metastasis as a component of the lung pre-metastatic niche (PMN) with two sides. It has been demonstrated that Toll-like Receptor4 (TLR4) can participate in signaling, such as NF-B and NLRP3, to facilitate tumor metastasis. A cellular membrane structural protein called caveolin-1 (CAV1) is associated with BC's proliferation, metastasis, and immunological control. According to our previous research, CAV1 on BC-derived sEVs facilitates the formation of the lung PMN by enhancing tenascin-C (TnC) secretion in lung fibroblasts to promote the deposition of ECM, by increasing the expression of PMN marker genes and inflammatory chemokines in lung epithelial cells, and by supporting N2-type polarization of lung macrophages via inhibiting the PTEN/CCL2/VEGF-A axis. More research is needed to determine how sEVs-mediated CAV1 facilitates BC-targeted metastasis to the lungs. By creating a stable-translocating cell line that stably interfered with CAV1 and a mouse model of BC lung metastasis, we investigated how sEVs-mediated CAV1 promotes BC lung metastasis and TAN recruitment and polarization in vivo and in vitro . In this study, we showed that CAV1 increases the likelihood that BC lung metastasis would occur by controlling the expression of integrin α6β4 and via boosting TANs recruitment and polarization through activating the TLR4-NF-B-IL-6/CCL2 and TLR4/NF-B/NLRP3 signaling pathways. According to our findings, CAV1 regulates integrin α6β4 and modulates TLR4 signaling, both of which are critical for BC lung metastasis. This finding may open new avenues for BC lung metastasis prevention and treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Rationale: Metastatic tumors in the stomach and small bowel are rare. This article reports a case of lung adenocarcinoma metastasizing to the stomach and small bowel., Patient Concerns: This case study presents the medical history of a 41-year-old male construction worker with a 1-month-long cough and slight chest discomfort. Imaging revealed a tumor in the right middle lobe of the lung, with metastasis to lymph nodes in the mediastinum and right hilar region, as well as a mass in the stomach's greater curvature and multiple lymph node metastases in the abdomen. Thirty-five days after the initial consultation, the patient exhibited worsening symptoms of vomiting and melena. A follow-up computed tomography scan revealed small bowel metastasis, leading to secondary intestinal obstruction and intussusception., Diagnoses: Biopsies confirmed poorly differentiated adenocarcinoma in the lung and stomach, with immunohistochemistry supporting a diagnosis of lung adenocarcinoma. Genetic testing showed no mutations or amplification in various genes., Interventions: The patient received interventional hemostatic treatment; however, the efficacy of the intervention was poor., Outcomes: The patient experienced worsening gastrointestinal symptoms. Despite attempted intervention, the patient ultimately died 78 days after seeking medical attention., Lessons: The case of lung cancer metastasizing to the stomach and small bowel presented in this article demonstrates high invasiveness and rapid progression. Combined with literature reports, this type of metastasis often indicates a poor prognosis for patients. The long-term benefits of surgical resection remain unclear, and further analysis will be needed with more cases and data in the future., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Liver cancer is the second leading cause of cancer-related deaths worldwide, motivating major scientific efforts to understand and treat this cancer type. Over 30% of patients with liver cancer progress to metastasis, which reduces the survival rate. Extensive studies on primary tumors have been conducted to improve the prognosis. However, there is a lack of appropriate and accessible models for studying the progression and metastasis of liver cancer. Moreover, conventional metastasis models do not reproduce metastasis as it occurs in patients. To address this lack of an appropriate model for the monitoring of cancer progression and evaluation of anticancer drugs, we established a spontaneous metastatic xenograft model using NSG mice subcutaneously transplanted with SK-Hep-1 cells. Compared to the conventional experimental metastasis model (intravenous transplantation), in which only lung metastasis was observed, the established spontaneous metastatic xenograft model was superior, as it showed both a primary tumor and metastatic patterns similar to those observed in human patients. Additionally, this model was successfully used to assess the antimetastatic efficacy of sorafenib. In conclusion, our results demonstrate that the established spontaneous metastatic xenograft model better reflects liver cancer metastasis and can be utilized to assess the efficacy of anticancer drugs for liver cancer., (© 2024. The Author(s).)

Background: Meningiomas are common central nervous system tumors, predominantly intracranial, they rarely develop extracranially. Moreover, benign meningiomas seldom metastasize., Case Presentation: This article presents a case report of a 55-year-old Chinese male patient with a primary World Health Organization grade 1 meningioma originating from the petrous apex of the temporal bone, accompanied by pulmonary metastasis. Following two incomplete resections of the primary tumor, the patient underwent radiotherapy and has since maintained a stable condition., Conclusion: The case report highlights the rare occurrence of pulmonary metastasis in a benign World Health Organization grade 1 meningioma originating from an extracranial site. It also illustrates the important role of radiotherapy in treating patients with meningioma. Additionally, a review of related literature is provided to gain insights for the diagnosis and treatment of the disease., (© 2024. The Author(s).)

Background: Lung cancer brain metastasis has a devastating prognosis, necessitating innovative treatment strategies. While chimeric antigen receptor (CAR) T-cell show promise in hematologic malignancies, their efficacy in solid tumors, including brain metastasis, is limited by the immunosuppressive tumor environment. The PD-L1/PD-1 pathway inhibits CAR T-cell activity in the tumor microenvironment, presenting a potential target to enhance therapeutic efficacy. This study aims to evaluate the impact of anti-PD-1 antibodies on CAR T-cell in treating lung cancer brain metastasis., Methods: We utilized a murine immunocompetent, syngeneic orthotopic cerebral metastasis model for repetitive intracerebral two-photon laser scanning microscopy, enabling in vivo characterization of red fluorescent tumor cells and CAR T-cell at a single-cell level over time. Red fluorescent EpCAM-transduced Lewis lung carcinoma cells ( EpCAM/tdt LL/2 cells) were implanted intracranially. Following the formation of brain metastasis, EpCAM-directed CAR T-cell were injected into adjacent brain tissue, and animals received either anti-PD-1 or an isotype control., Results: Compared to controls receiving T-cell lacking a CAR, mice receiving EpCAM-directed CAR T-cell showed higher intratumoral CAR T-cell densities in the beginning after intraparenchymal injection. This finding was accompanied with reduced tumor growth and translated into a survival benefit. Additional anti-PD-1 treatment, however, did not affect intratumoral CAR T-cell persistence nor tumor growth and thereby did not provide an additional therapeutic effect., Conclusion: CAR T-cell therapy for brain malignancies appears promising. However, additional anti-PD-1 treatment did not enhance intratumoral CAR T-cell persistence or effector function, highlighting the need for novel strategies to improve CAR T-cell therapy in solid tumors., (© 2024. The Author(s).)

Objective: The aim of this study was to evaluate the CT features of pulmonary metastases in dogs with hemangiosarcoma (HSA) at various sites. Additionally, the CT characteristics of extrapulmonary metastases in the same population were assessed., Methods: Retrospective, observational, and descriptive study conducted from April 2013 to January 2024. Dogs with histologically confirmed HSA and suspected or cytologically/histologically confirmed lung metastases were included. Dogs were excluded if they had a second primary tumor or only 1 unsampled pulmonary nodule., Results: 33 dogs were included, with 26/33 [78.8%] having more than 10 metastatic pulmonary nodules. Most nodules were generalized (24/33 [72.7%]), miliary (29/33 [87.9%]) to subcentimetric (32/33 [97%]) in size, well-defined margins (29/33 [87.9%]), or a perilesional halo sign (24/33 [72.7%]). When more than 10 nodules were present, a generalized distribution was prevalent, while a peripheral location was more common when 2 to 10 nodules were present (P < .0001). In 32/33 (97%) cases, a pulmonary vessel was directly connected to the nodule (feeding vessel). After contrast administration, most lung metastases appeared homogenous (26/33 [78.8%]), although some showed areas of intense enhancement (5/33 [15.1%]) a feature also observed in extrapulmonary metastases with varying frequency (0% to 85.7%)., Conclusions: Pulmonary HSA metastases were characterized by generalized, small (miliary/subcentimetric), well-defined nodules, commonly associated with a halo sign and feeding vessel. Intralesional areas of spotty postcontrast linear or amorphous strong hyperdensity were frequently observed especially in extrapulmonary metastases., Clinical Relevance: These features may help radiologists and clinicians orient their diagnosis toward metastatic HSA.

In the process of tumor metastasis, tumor cells can acquire invasion by excessive uptake of nutrients and energy and interact with the host microenvironment to shape a premetastatic niche (PMN) that facilitates their colonization and progression in the distal sites. Pyruvate is an essential nutrient that engages in both energy metabolism and remodeling of the extracellular matrix (ECM) in the lungs for PMN formation, thus providing a target for tumor metastasis treatment. There is a paucity of strategies focusing on PMN prevention, which is key to metastasis inhibition. Here, we design a bioresponsive nanoparticle (HP/GU) based on a disulfide-cross-linked hyperbranched polyethylenimine (D-PEI) core and a hyaluronic acid (HA) shell with a reactive oxygen species (ROS)-sensitive cross-linker between them to encapsulate glucose oxidase (GOX) and a mitochondrial pyruvate carrier (MPC) inhibitor via electrostatic interaction, which reinforces starvation therapy and reduces PMN formation in the lungs via inhibiting pyruvate metabolism. In tumor cells, GOX and MPC inhibitors can be rapidly released and synergistically reduce the energy supply of tumor cells by consuming glucose and inhibiting pyruvate uptake to decrease tumor cell invasion. MPC inhibitors can also reduce ECM remodeling by blocking cellular pyruvate metabolism to prevent PMN formation. Consequently, HP/GU achieves an efficient inhibition of both primary and metastatic tumors and provides an innovative strategy for the treatment of tumor metastases.

Metastatic disease results from the dissemination of tumor cells beyond their organ of origin to grow in distant organs and is the primary cause of death in patients with advanced breast cancer. Preclinical murine models in which primary tumors spontaneously metastasize are valuable tools for studying metastatic progression and novel cancer treatment combinations. Here, we characterize a novel syngeneic murine breast tumor cell line that provides a model of spontaneously metastatic neu-expressing breast cancer with quicker onset of widespread metastases after orthotopic mammary implantation in immune-competent NeuN mice. The NT2.5-lung metastasis (-LM) cell line was derived from serial passaging of tumor cells that were macro-dissected from spontaneous lung metastases after orthotopic mammary implantation of parental NT2.5 cells. Within one week of NT2.5-LM implantation, metastases are observed in the lungs. Within four weeks, metastases are also observed in the bones, spleen, colon, and liver. We demonstrate that NT2.5-LM metastases are positive for NeuN-the murine equivalent of human epidermal growth factor 2 (HER2). We further demonstrate altered expression of markers of epithelial-to-mesenchymal transition (EMT), suggestive of their enhanced metastatic potential. Genomic analyses support these findings and reveal enrichment in EMT-regulating pathways. In addition, the metastases are rapidly growing, proliferative, and responsive to HER2-directed therapy. The new NT2.5-LM model provides certain advantages over the parental NT2/NT2.5 model, given its more rapid and spontaneous development of metastases. Besides investigating mechanisms of metastatic progression, this new model may be used for the rationalized development of novel therapeutic interventions and assessment of therapeutic responses., (© 2024. The Author(s).)

Patients with triple-negative breast cancer (TNBC) have an increased propensity to develop lung metastasis. Our previous studies demonstrated that stem-like ALDH hi CD44 + breast cancer cells interact with lung-derived soluble factors, resulting in enhanced migration and lung metastasis particularly in TNBC models. We have also observed that the presence of a primary TNBC tumor can 'prime' the lung microenvironment in preparation for metastasis. In this study, we hypothesized that soluble lung-derived factors secreted in the presence of a primary TNBC tumor can influence stemness/plasticity of breast cancer cells. Using an ex vivo pulmonary metastasis assay (PuMA), we observed that the lung microenvironment supports colonization and growth of ALDH hi CD44 + TNBC cells, potentially via interactions with lung-derived FGF2. Exposure of TNBC cells to lung-conditioned media (LCM) generated from mice bearing TNBC primary tumors (tbLCM) significantly enhanced the proportion of ALDH hi CD44 + cells compared to control or LCM from tumor-naïve mice (tnLCM). Further analysis using a human cancer stem cell qPCR array revealed that, relative to tnLCM or control, exposure of TNBC cells to tbLCM leads to downregulation of the transcription factor and putative tumor suppressor Dachshund homolog 1 (DACH1), a downstream regulator of FGF2. In addition, inhibition of DACH1 using siRNA or treatment with recombinant FGF2 enhanced the ALDH hi CD44 + phenotype. Taken together, our findings suggest that the FGF2-DACH1 signaling axis supports stemness/plasticity of TNBC cells in the lung microenvironment and lays the foundation for future evaluation of FGF2 as a potential novel therapeutic target for treatment or prevention of breast cancer metastasis to the lung., (© 2024. The Author(s).)

The presence of metastatic cancer represents a high-risk condition for the treatment of heart disease requiring surgical or percutaneous procedures. We present the case of a 58-year-old man with pulmonary adenocarcinoma and renal metastases surviving more than 3 years after chemotherapy and immunotherapy suffering dyspnea and chest pain on minimal exertion due to 99% anterior coronary artery stenosis associated with severe aortic stenosis of a bicuspid valve. We treated the cardiac lesions in two steps by coronary angioplasty with drug-eluting stent implantation followed by percutaneous prosthetic aortic valve replacement. The procedures were successful with resolution of the symptoms and recovery of the usual ECOG-PS 0-1 functional capacity which persists 24 months after cardiac procedures. This case demonstrates that the multidisciplinary collaboration between oncologists and cardiologists with a personalized patient-centered approach allows to treat complex clinical situations successfully in the emerging category of patients surviving with metastatic cancer.

Objectives: To evaluate the performance of artificial intelligence (AI) in the preoperative detection of lung metastases on CT., Materials and Methods: Patients who underwent lung metastasectomy in our institution between 2016 and 2020 were enrolled, their preoperative CT reports having been performed before an AI solution (Veye Lung Nodules, version 3.9.2, Aidence) became available as a second reader in our department. All CT scans were retrospectively processed by AI. The sensitivities of unassisted radiologists (original CT radiology reports), AI reports alone and both combined were compared. Ground truth was established by a consensus reading of two radiologists, who analyzed whether the nodules mentioned in the pathology report were retrospectively visible on CT. Multivariate analysis was performed to identify nodule characteristics associated with detectability., Results: A total of 167 patients (men: 62.9 %; median age, 59 years [47-68]) with 475 resected nodules were included. AI detected an average of 4 nodules (0-17) per CT, of which 97 % were true nodules. The combination of radiologist plus AI (92.4 %) had significantly higher sensitivity than unassisted radiologists (80.4 %) (p < 0.001). In 27/57 (47.4 %) patients who had multiple preoperative CT scans, AI detected lung nodules earlier than the radiologist. Vascular contact was associated with non-detection by radiologists (OR:0.32[0.19, 0.54], p < 0.001), whilst the presence of cavitation (OR:0.26[0.13, 0.54], p < 0.001) or pleural contact (OR:0.10[0.04, 0.22], p < 0.001) was associated with non-detection by AI., Conclusion: AI significantly increases the sensitivity of preoperative detection of lung metastases and enables earlier detection, with a significant potential benefit for patient management., 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 B.V.)

In this report, we describe a very rare case of metastatic epithelioid hemangio-endothelioma (EHE) originating from other organs such as the lung and requiring craniotomy due to subsequent hemorrhage. A 50-year-old man was diagnosed with EHE in the bilateral lungs, the mediastinum, and the right adrenal gland 8 years earlier. One year earlier, he had developed spinal metastasis. Six months earlier, a screening brain MRI had revealed multiple brain metastases of tumor. He developed subcortical hemorrhage from the tumor in the right parietal lobe and successfully underwent removal of hematoma and tumor. Histopathological examinations revealed EHE. Metastatic EHE is very rare but may be at high risk of intracranial hemorrhage. It is quite important to consider the possibility of brain metastasis and subsequent bleeding when treating patients with EHE., (© 2024 Japanese Society of Neuropathology.)

Lung cancer is a type of cancer that can metastasize to the lungs, brain, bones, liver, adrenal glands, and other organs; however, the occurrence of brain metastases is the most common event. Symptoms of brain metastasis include motor dysfunction, mental dysfunction, seizures, headaches, nausea, and vomiting, and significantly reduce the quality of life of cancer patients. Brain metastases are a poor prognostic factor, and controlling them is extremely important for prolonging prognosis and improving the quality of life. Currently, local surgery and radiotherapy are recommended for their treatment. However, recently, cancer treatments using molecular-targeted drugs and immune checkpoint inhibitors have been introduced, which may also be effective against brain metastases. Therefore, it is necessary to determine whether local or systemic therapy is optimal for each case. In this review, we focus on recent findings regarding drug therapy in treating brain metastases from advanced non-small cell lung cancer., (© 2024. The Author(s).)

Background: Small cell lung cancer (SCLC) harbours the most aggressive phenotype of all lung cancers to correlate with its bleak prognosis. The aggression of SCLC is partially attributable to its strong metastatic tendencies. The biological processes facilitating the metastasis in SCLC are still poorly understood and garnering a deeper understanding of these processes may enable the exploration of additional targets against this cancer hallmark in the treatment of SCLC., Recent Findings: This narrative review will discuss the proposed molecular mechanisms by which the cancer hallmark of activating invasion and metastasis is featured in SCLC through important steps of the metastatic pathway, and address the various molecular targets that may be considered for therapeutic intervention. The tumour immune microenvironment plays an important role in facilitating immunotherapy resistance, whilst the poor infiltration of natural killer cells in particular fosters a pro-metastatic environment in SCLC. SCLC vasculogenesis is achieved through VEGF expression and vascular mimicry, and epithelial-mesenchymal transition is facilitated by the expression of the transcriptional repressors of E-cadherin, the suppression of the Notch signalling pathway and tumour heterogeneity. Nuclear factor I/B, selectin and B1 integrin hold important roles in SCLC migration, whilst various molecular markers are expressed by SCLC to assist organ-specific homing during metastasis. The review will also discuss a recent article observing miR-1 mRNA upregulation as a potential therapeutic option in targeting the metastatic activity of SCLC., Conclusion: Treatment of SCLC remains a clinical challenge due to its recalcitrant and aggressive nature. Amongst the many hallmarks used by SCLC to enable its aggressive behaviour, that of its ability to invade surrounding tissue and metastasise is particularly notable and understanding the molecular mechanisms in SCLC metastasis can identify therapeutic targets to attenuate SCLC aggression and improve mortality., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

The primary treatment for nasopharyngeal carcinoma (NPC) is radiotherapy. In rare cases, patients with NPC treated with radiotherapy may develop radiation-induced sarcoma (RIS), a malignant tumor, in the field of previous radiation. The prognosis is poor, and complete surgical resection is the only potentially curative treatment. We report a case of radiation-induced nasopharyngeal sarcoma after radiotherapy for NPC with suspected lung and liver metastases in a 69-year-old woman., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Current guidelines recommend against the use of routine imaging tests to detect distant metastasis in asymptomatic breast cancer patients. However, recent advancements in effective therapeutics and diagnostic accuracy have raised the need to reassess the clinical efficacy of intensive metastasis surveillance. We report the results of a multicenter retrospective study to investigate the association between intensive imaging studies and survival outcomes., Patients and Methods: We retrospectively reviewed the data of 4130 patients who underwent surgery from 11 hospitals in Korea between January 2010 and December 2011. Patients were divided into two groups on the basis of the intensity of metastasis imaging studies during their disease-free period. The types and intervals of the imaging studies were based on each physician's decisions., Results: High-intensive screening showed a shorter distant metastasis-free survival [p < 0.001, hazard ratio (HR) 1.62; 95% confidence interval (CI) 1.29-2.04], especially for patients in whom bone or lung was the first site of metastasis. With a median follow-up period of 110.0 months, the 5-year breast cancer-specific survival (BCSS) rate was 96.5%. The high-intensity screening group showed significantly poorer BCSS compared with the low-intensity screening group (p < 0.001, HR 3.13; 95% CI 2.32-4.21). However, both multivariable analysis and propensity score matching analysis showed no significant association between the screening intensity and BCSS., Conclusions: Frequent imaging studies to detect distant metastasis were associated with earlier detection of distant metastasis, especially for lung and bone metastasis. However, intensive surveillance showed no apparent association with BCSS despite the use of currently available treatments., (© 2024. The Author(s).)

Objectives: Investigation of the therapeutic effect of zoledronic acid (ZA) in a preclinical model of jaw osteosarcoma (JO)., Materials and Methods: The effect of 100 μg/kg ZA administered twice a week was assessed in a xenogenic mouse model of JO. The clinical (tumor growth, development of lung metastasis), radiological (bone microarchitecture by micro-CT analysis), and molecular and immunohistochemical (TRAP, RANK/RANKL, VEGF, and CD146) parameters were investigated., Results: Animals receiving ZA exhibited an increased tumor volume compared with nontreated animals (71.3 ± 14.3 mm 3 vs. 51.9 ± 19.9 mm 3 at D14, respectively; p = 0.06) as well as increased numbers of lung metastases (mean 4.88 ± 4.45 vs. 0.50 ± 1.07 metastases, respectively; p = 0.02). ZA protected mandibular bone against tumor osteolysis (mean bone volume of 12.81 ± 0.53 mm 3 in the ZA group vs. 11.55 ± 1.18 mm 3 in the control group; p = 0.01). ZA induced a nonsignificant decrease in mRNA expression of the osteoclastic marker TRAP and an increase in RANK/RANKL bone remodeling markers., Conclusion: The use of bisphosphonates in the therapeutic strategy for JO should be further explored, as should the role of bone resorption in the pathophysiology of the disease., (© 2024 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Metastasis is the primary stumbling block to the treatment of bladder cancer (BC). In order to spread, tumor cells must acquire increased migratory and invasive capacity, which is tightly linked with pseudopodia formation. Here, we unravel the effects of sulforaphane (SFN), an isothiocyanate in cruciferous vegetables, on the assembly of pseudopodia and BC metastasis, and its molecular mechanism in the process. Our database analysis revealed that in bladder tumor, pseudopodia-associated genes, CTTN, WASL and ACTR2/ARP2 are upregulated. SFN caused lamellipodia to collapse in BC cells by blocking the CTTN-ARP2 axis. SFN inhibited invadopodia formation and cell invasion by reducing WASL in different invasive BC cell lines. The production of ATP, essential for the assembly of pseudopodia, was significantly increased in bladder tumors and strongly inhibited by SFN. Overexpressing AKT1 reversed the downregulation of ATP in SFN-treated bladder cancer cells and restored filopodia and lamellipodia morphology and function. Bioluminescent imaging showed that SFN suppressed BC metastases to the lung of nude mice while downregulating Cttn and Arp2 expression. Our study thus reveals mechanisms of SFN action in inhibiting pseudopodia formation and highlights potential targeting options for the therapy of metastatic bladder cancer., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To evaluate whether patient factors affect development of non-pulmonary soft-tissue metastases following treatment of canine appendicular osteosarcoma and to report and compare outcomes to those in dogs with pulmonary or osseous metastases., Animals and Procedure: The records of 3 veterinary teaching hospitals were reviewed to identify dogs that received definitive treatment for a primary appendicular osteosarcoma lesion and chemotherapy between January 2010 and June 2022. Dogs with non-pulmonary metastases following initial treatment were included. Descriptive statistics were calculated to summarize signalment information, and metastasis and survival times were compared between groups using Kaplan-Meier survival analysis and log-rank tests., Results: Thirty-six and 109 dogs developed non-pulmonary soft-tissue metastases and pulmonary or osseous metastases, respectively, following initial treatment. No patient factors were significantly associated with development of non-pulmonary soft-tissue metastases. The median times to non-pulmonary soft-tissue metastasis or initial pulmonary or osseous metastasis were 220 and 169 d, respectively ( P = 0.18); whereas overall median survival times were 250 and 270 d, respectively ( P = 0.36)., Conclusion: Dogs with non-pulmonary soft-tissue metastases had similar disease-free intervals and survival rates to dogs with typical pulmonary or osseous metastases., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

For cancer metastasis inhibition, the combining of nanozymes with immune checkpoint blockade (ICB) therapy remains the major challenge in controllable reactive oxygen species (ROS) generation for creating effective immunogenicity. Herein, new nanozymes with light-controlled ROS production in terms of quantity and variety are developed by conjugating supramolecular-wrapped Fe single atom on iridium metallene with lattice-strained nanoislands (FeSA-Ir@PF NSs). The Fenton-like catalysis of FeSA-Ir@PF NSs effectively produced •OH radicals in dark, which induced ferroptosis and apoptosis of cancer cells. While under second near-infrared (NIR-II) light irradiation, FeSA-Ir@PF NSs showed ultrahigh photothermal conversion efficiency (𝜂, 75.29%), cooperative robust •OH generation, photocatalytic O 2 and 1 O 2 generation, and caused significant pyroptosis of cancer cells. The controllable ROS generation, sequential cancer cells ferroptosis and pyroptosis, led 99.1% primary tumor inhibition and multi-immunogenic responses in vivo. Most importantly, the inhibition of cancer lung metastasis is completely achieved by FeSA-Ir@PF NSs with immune checkpoint inhibitors, as demonstrated in different mice lung metastasis models, including circulating tumor cells (CTCs) model. This work provided new inspiration for developing nanozymes for cancer treatments and metastasis inhibition., (© 2024 Wiley‐VCH GmbH.)