Lung Metastasis Research Articles

Engineered manganese-BODIPY coordinated nanoadjuvants for enhanced NIR-II photo-metalloimmunotherapy

Immunotherapy, a pivotal and promising approach for tumor treatment, has demonstrated prominent clinical efficacy. However, its effectiveness is often impeded by insufficient antitumor immune responses attributed to the immunosuppressive tumor microenvironment (TME). The combination of immune activation through the stimulator of interferon genes (STING) pathway and phototherapy holds great potential for surmounting this challenge in advanced tumor immunotherapy. Herein, a novel manganese-boosted NIR-II photo-metalloimmunotherapy is proposed to synergistically enhance antitumour efficacy by fabricating Mn2+-BODIPY-based coordinated photo-immune nanoadjuvants (BMR), modified with tumor-targeted peptide cRGD. The obtained BMR could effectively deliver Mn2+ to tumor sites, and immunogenic cell death (ICD) was evoked by localized photothermal ablation of tumors using NIR-II laser irradiation. Simultaneously, pH-responsive release of Mn2+ would trigger the activation of STING pathway to promote the production of type I interferons (I-IFNs), significantly facilitating the maturation of dendritic cells (DCs) and polarization of macrophages to M1 phenotypes. Furthermore, by synergistically initiating systematic and robust antitumour immune responses, the BMR-mediated NIR-II photo-metalloimmunotherapy achieved remarkable therapeutic efficacy against both primary and lung metastasis of B16F10 tumors. Overall, in light of the versatile functionalities and synthetic flexibility of coordinated nanoadjuvants, formulated with photofunctional ligands and diverse metal ions, this work provides new insights into the design of metal coordination nanomedicine for effective antitumor photo-metalloimmunotherapy.

Metabolic Acidity/H2O2 Dual-Cascade-Activatable Molecular Imaging Platform Toward Metastatic Breast Tumor Malignancy.

Fluorescence imaging in the second near-infrared window (NIR-II) is crucial for accurate tumor diagnosis, offering superior resolution and penetration capabilities. Current NIR-II probes are limited by either being "always on" or responding to one stimulus, leading to low signal-to-noise ratios and potential false positives. We introduced a dual-lock-controlled probe, HN-PBA, activated by both H2O2 and tumor acidic environment. This dual response ensures bright fluorescence at tumor sites, leading to higher tumor-to-normal tissue ratios (T/NT) compared to conventional "always on" probes and probes activated only by H2O2. This strategy allows precise tumor identification and removal of primary and metastatic tumors, achieving superior T/NT ratios (24.3/6.4 for orthotopic and lung metastasis, respectively). Our probe also effectively detected lung metastatic foci as small as≤0.7 mm and showed the capability for accurate lesion localization in clinical breast cancer specimens. This dual-stimuli-responsive strategy could aid future diagnostic probe design.

Homeostatic self-MHC-I recognition regulates anti-metastatic function of mature lung natural killer cells

Natural killer (NK) cells are important innate immune effector cells for controlling tumor growth and metastasis. Differentiated mature NK cells preferentially reside in the peripheral tissues and express higher levels of self-major histocompatibility complex class I (MHC-I)-recognizing inhibitory receptors. MHC-I recognition by NK cells are known to be important for their development and maturation processes, however, the role of homeostatic MHC-I recognition in maintaining effector functions of mature NK cells in the peripheral tissues needs to be elucidated. In this study, we utilized a pan anti-MHC-I blocking monoclonal antibody (anti-MHC-I) to examine the role of homeostatic MHC-I recognition in the response of pulmonary mature NK cells in an experimental lung metastasis model of B16F10 melanoma. Anti-MHC-I treatment showed significant inhibition of the lung metastasis of B16F10 melanoma in NK cell- and IFN-γ-dependent mechanisms. The blockade of homeostatic MHC-I recognition increased mature lung NK cell responsiveness, such as direct cytotoxicity and IFN-γ production, rather than the number of lung NK cells. Mechanistically, the gene expression of activating receptors including DNAX accessory molecule-1 (DNAM-1) was upregulated in NK cells treated with anti-MHC-I, and further the enhanced NK cell cytotoxicity against B16F10 cells was DNAM-1-dependent. Collectively, homeostatic self-MHC-I recognition regulates anti-metastatic function of mature lung NK cells by restraining the expression of activating receptors.

Jing-Si herbal tea attenuates oral cancer cell viability, migration, and invasion by regulating epithelial-to-mesenchymal transition and reactive oxygen species accumulation

IntroductionOral cancer is the sixth most common cancer worldwide and can be life-threatening if not diagnosed and treated in its early stages. Jing-Si herbal tea (JSHT), containing eight traditional Chinese medicine-based herbs, is known to suppress the malignancy, growth, and metastasis of several tumour cells, including breast, lung, and colon cancer cells. However, the pharmacological effect of JSHT on oral cancer progression is still unclear. MethodsIn this study, we evaluated the potential of JSHT to arrest the development of oral cancer via induction of cell death by reactive oxygen species (ROS) accumulation and inhibition of migration, invasion, and epithelial-to-mesenchymal transition (EMT). For this purpose, we employed the human tongue squamous cell carcinoma human tongue squamous carcinoma cell line, which we treated with different JSHT concentrations for 24 hours, and assessed cell viability, migration, and wound healing capabilities, together with western blotting for measuring expression levels of EMT markers. ResultsSurvival, migration/invasion ability, EMT, and ROS production in the human tongue squamous carcinoma human tongue squamous carcinoma and FaDu human pharynx squamous cell carcinoma cell line were decreased by JSHT treatment via Lon protease-independent mechanisms. ConclusionThis study demonstrates that JSHT could be regarded as a candidate new supplement to existing anticancer therapies and an alternative, orally administered healthcare product for treating oral squamous cell carcinoma.

The Role of Anesthetic Management in Lung Cancer Recurrence and Metastasis: A Comprehensive Review.

Lung cancer remains a leading cause of cancer-related mortality worldwide. Although surgical treatment is a primary approach, residual cancer cells and surgery-induced pathophysiological changes may promote cancer recurrence and metastasis. Anesthetic agents and techniques have recently been shown to potentially impact these processes by modulating surgical stress responses, immune function, inflammatory pathways, and the tumor microenvironment. Anesthetics can influence immune-modulating cytokines, induce pro-inflammatory factors such as HIF-1α, and alter natural-killer cell activity, affecting cancer cell survival and spread. Preclinical studies suggest volatile anesthetics may promote tumor progression by triggering pro-inflammatory signaling, while propofol shows potential antitumor properties through immune-preserving effects and reductions in IL-6 and other inflammatory markers. Additionally, opioids are known to suppress immune responses and stimulate pathways that may support cancer cell proliferation, whereas regional anesthesia may reduce these risks by decreasing the need for systemic opioids and volatile agents. Despite these findings, clinical data remain inconclusive, with studies showing mixed outcomes across patient populations. Current clinical trials, including comparisons of volatile agents with propofol-based total intravenous anesthesia, aim to provide clarity but highlight the need for further investigation. Large-scale, well-designed studies are essential to validate the true impact of anesthetic choice on cancer recurrence and to optimize perioperative strategies that support long-term oncologic outcomes for lung cancer patients.

PTPN20 promotes metastasis through activating NF-κB signaling in triple-negative breast cancer

BackgroundCancer metastasis remains a major challenge in the clinical management of triple-negative breast cancer (TNBC). The NF-κB signaling pathway has been implicated as a crucial factor in the development of metastases, but the underlying molecular mechanisms remain largely unclear.MethodsPTPN20 expression was evaluated using data from the Sweden Cancerome Analysis Network-Breast and The Cancer Genome Atlas database, as well as by western blotting and immunohistochemistry in 88 TNBC patients. The ability of PTPN20 to activate NF-κB was assessed by luciferase reporter assays. The effects of PTPN20 overexpression and knockdown via short hairpin RNA were examined in TNBC cell lines by wound healing and transwell matrix penetration assays. Additionally, we analyzed the growth and metastasis abilitiy of 4T1 xenograft tumors in nude mice.ResultsPTPN20 levels were elevated in TNBC cell lines and patient samples compared to controls, and higher protein levels correlated with metastasis-free survival. Overexpression of PTPN20 enhanced migration and invasion in vitro, and promoted lung metastasis in vivo. Our finding revealed that PTPN20 activates NF-κB signaling by dephosphorylating p65 at Ser468, preventing its binding to COMMD1, thereby protecting p65 from degradation. Downregulation of PTPN20 effectively inhibit, while p65 S468A mutant restored the migratory and invasive abilities of TNBC cells.ConclusionsCollectively, our results demonstrate that PTPN20 plays a critical role in TNBC metastasis through the activation of NF-κB signaling. We propose that PTPN20 may serve as a novel prognostic marker and potential therapeutic target for the treatment of TNBC.

A Retrospective Analysis of Real-Life Management of Colorectal Cancer Lung-Limited Metastases Treated with Surgery: Outcomes and Prognostic Factors.

Background: Unlike liver metastases, the role of surgery in colorectal cancer lung-limited metastases (CCLLM) is not yet established, and data are still poor. We performed a retrospective analysis to evaluate the impact of surgery on the management of CCLLM. Material and Method: We retrospectively analyzed patients who received surgery for CCLLM at our Institution from January 2010 to June 2019. The aim of the study was to evaluate the impact of clinical and pathological features on the survival (OS and DFS) of patients treated with surgery for CCLLM. Results: One hundred and fifty patients were included in the analysis. Seventy-six patients received preoperative chemotherapy (pCT) and 56 an adjuvant treatment (aCT), while 18 underwent up-front surgery without CT. In the whole population, median OS (mOS) and median DFS (mDFS) were 54.1 months (95%CI 44.0-82.1) and 24.0 months (95%CI 20.0-31.2), respectively. In multivariate analysis, number of metastases was the only factor correlated to DFS (p = 0.0006) and OS (p = 0.0018). Conclusion: Our study, although retrospective and of small size, shows that tumor burden (number of metastases) is the main prognostic factor in patients undergoing lung surgery for CCLLM. Moreover, our results suggest that surgery for lung metastases might prolong survival. These data strengthen the role of multidisciplinary management to allow patients with CCLLM to pursue local treatment whenever possible, even regardless of previous liver surgery or RAS mutated status.

A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy

Cancer immunotherapy remains a low immune response rate in clinic because of dominant immunosuppressive tumor microenvironment (TME) and lack of effective drug to specifically remodel the TME. In this work, we introduced a tumor-seeking human serum albumin (HSA) based delivery platform by covalently conjugating with a tumor-targeting near-infrared (NIR) photosensitizer (IR-DBI) and non-covalently loading of immune modulator Resiquimod (R848). HSA exhibited tumor-preferential accumulation after covalent conjugation with IR-DBI. Meanwhile, HSA restricted the rotation of IR-DBI, narrowed the HOMO-LUMO energy gap, significantly enhanced fluorescent intensity and dual-modal phototherapy (PTT/PDT). The enhanced phototherapeutic effect further induced robust ICD effect. More importantly, non-covalent loading of R848 could be released from HSA at tumor sites by laser irradiation-induced heat. The in-situ release of R848 in TME efficiently promoted the maturation of DC cells and repolarized M2 macrophages to M1 macrophages. Consequently, robust photo-induced antitumor immunity was triggered in the different mice models bearing primary and distant tumors or lung metastasis, which was further enhanced by combining with CTLA-4 blockade therapy. Taken together, this work may present a versatile albumin composite which exhibits tumor-preferential accumulation and imaging-guided PDT/PTT/immunotherapy.

Curative-intent surgery for solitary bone metastasis from extremity and trunk wall sarcoma: What are the outcomes and complications?

IntroductionApproximately 40–50 % of sarcoma patients will develop lung metastasis, but only 10 % will develop bone metastasis. The survival benefit of surgery for solitary bone metastasis remains unclear. MethodsFrom 1987 to 2019, 47 patients who underwent curative-intent treatment for localized bone or soft tissue sarcoma in the extremities or trunk wall developed solitary bone metastases as the first distant recurrence. Of them, 51 % (24/47) received curative-intent metastasectomy. We compared the clinicopathologic characteristics of the metastasectomy versus non-metastasectomy patients and evaluated the prognostic impact of solitary bone metastasectomy. The primary outcome measure was disease-specific survival (DSS) after developing solitary bone metastasis. ResultsThe post-metastasis DSS was worse with larger primary tumour size (HR 1.09; 95 % CI 1.02–1.16; p = 0.01) and bone metastasis in the pelvis or spine versus other bones (HR 3.79, 95 % CI 1.46–9.87; p = 0.01), and better with curative-intent surgery for the solitary bone metastasis (HR 0.14; 95 % CI 0.06–0.34; p < 0.001). The median DSS was 43 (95 % CI, 24–69) months for the metastasectomy group vs. 13 (95 % CI, 7–19) months for the non-metastasectomy group (p < 0.001). The metastasectomy group had fewer patients with metastasis in the spine or pelvis and longer metastasis-free interval. In the multivariate analysis, curative-intent surgery for solitary bone metastasis was associated with better survival (HR 0.21; 95 % CI 0.08–0.53; p = 0.001). ConclusionsCurative-intent surgery for solitary bone metastasis from sarcoma is associated with a better prognosis and is a reasonable treatment strategy whenever feasible.

Blood lipid profiles associated with metastatic sites in advanced gastric cancer

BackgroundThis study explored the correlation between peripheral blood lipid levels and clinicopathological parameters in patients with advanced gastric cancer (GC), focusing on changes in lipid levels during disease progression.MethodsPathological features and serum lipid profiles of 179 patients with stage III-IV gastric adenocarcinoma were analyzed. Lipid parameters examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein AI (Apo AI), apolipoprotein B (Apo B), lipoprotein(a) (Lp(a)), among others. The total cholesterol-lymphocyte score (TL score) and BMI were also calculated. The association between lipid parameters and clinicopathological characteristics such as age, gender, family history, and metastasis sites was assessed.ResultsIn GC patients, females had higher TG levels than males. Patients with peritoneal metastasis had significantly lower levels of TC, LDL-C, Apo B, and B/A ratio. Those with lung metastasis exhibited higher LDL-C levels and lower levels of VLDL-C. No significant associations were found between lipid levels and metastasis to distant lymph nodes, liver, or bone. Female patients with ovarian metastasis had significantly lower VLDL-C levels. Multivariate analysis revealed low TC as an independent risk factor for peritoneal metastasis, high LDL-C and low VLDL-C levels for lung metastasis, and younger age and low VLDL-C for ovarian metastasis.ConclusionSpecific blood lipid levels are significantly associated with metastatic sites in advanced gastric cancer. Lipid profiles could serve as potential biomarkers for predicting metastatic sites in GC patients.

Advanced Malignant Melanoma of the Vulva in a 70 years old woman

Vulvar melanoma is a rare malignant tumor of the female genital tract tend to occur in older age women and a high tendency to metastasize because the diagnosis is usually delayed (1). In this case report, we present a 70-year-old para 8 woman who presented with progressively increasing vulvar swelling of 2 years and multiple visit to health institution. Examination revealed 7cm diameter multi-nodular mass with areas of dark and dark blue-violet color filling the introitus that involves the clitoris, labia minora, lower third of the anterior vagina and urethra. Incisional biopsy from the mass showed malignant melanoma. Imaging with CT scan revealed bilateral lung metastasis. Palliative chemotherapy was planned but the patient lost to follow up.

Incidence and gender difference of brain metastases in newly diagnosed follicular thyroid cancer patients.

Population-based estimates of brain metastases in follicular thyroid cancer (FTC) patients with or without distant metastases (DMs) at diagnosis are lacking. To study the prevalence of brain metastases in FTC patients and compare gender disparity. DMs are defined as bone, lung, and brain metastases. Using the SEER database, we identified 5116 patients diagnosed with FTC between 2010 and 2019. The incidences of brain metastases were calculated for the entire cohort and among patients with bone/lung metastases. Cohorts were stratified by gender and age. 4.8% (245) had DMs at diagnosis, primarily in the form of bone metastases (3.6%), followed by lung metastases (2.4%). The incidence of brain metastases at initial diagnosis was only 0.37% (17 females and 2 males), but occurred in 8.2% and 6.1% of patients with bone metastases and lung metastases, respectively. Median survival for patients with brain metastases was only 8.0 months (95% CI, 4.1-11.9). Interestingly, female patients with bone metastases exhibited a significantly higher incidence of brain metastases compared to males (12.0% vs. 1.5%), with a notable odds ratio of 8.971 (95% CI:1.152-69.835) in univariate analysis. Multivariate logistic regression analysis confirmed that being female (odds ratio, 10.08; 95% CI:1.243-81.748) was the sole statistically significant risk factor for brain metastases in FTC patients with bone metastases at diagnosis. An incidence of brain metastases is observed in newly diagnosed FTC patients with DMs, especially in females with bone involvement. Our findings advocate for the early detection of brain metastases in female FTC patients with concurrent bone metastases at diagnosis.

Fruquintinib Combined With PD-1 Inhibitors for the Treatment of the Patients With Microsatellite Stability Metastatic Colorectal Cancer: Real-world Data

BackgroundProgrammed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors have shown limited effectiveness in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Combining anti-angiogenesis inhibitors with PD-1 inhibitors has the potential to reverse the immunosuppressive tumor microenvironment, synergistically enhancing the antitumor immune response in MSS mCRC. The goal is to present real-world data that prove the clinical efficacy and safety of fruquintinib combined with PD-1 inhibitors in MSS mCRC. Materials and methodsWe conducted a real-world retrospective study in patients with MSS mCRC who received treatment with fruquintinib combined with PD-1 inhibitors between May 2019 and March 2023 in our center. Results77 patients with MSS mCRC received fruquintinib combined with PD-1 inhibitors. In total, 5.2% of patients (4/77) achieved a partial response (PR), while 50.6% (39/77) had a stable disease (SD). Notably, three lesions achieving PR were all lung metastases and the overall disease control rate (DCR) reached 55.8% (43/77). Median progression-free survival (PFS) and overall survival (OS) reached 5.1 months (95% CI:3.6-6.7) and 14.6 months (95% CI:9.6-15.6), respectively. Multivariate Cox analysis showed that prior treatment without vascular endothelial growth factor (VEGF) inhibitors was significantly associated with PFS and OS (p<0.05). Further analysis indicated that total- or polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) significantly decreased after treatment (p=0.039), especially in the PR/SD group (p=0.003). Most adverse events included abdominal pain, rash, edema, diarrhea, and immunotherapy-associated hypothyroidism, yet symptoms were controllable. ConclusionOur results provided additional evidence that patients with MSS mCRC could benefit from the combination of fruquintinib and PD-1 inhibitors, especially those with lung metastases or without prior treatment with VEGF inhibitors. The detection of MDSCs may be an immune indicator for predicting of the combined therapy.

Establishment and Validation of a Prognostic Nomogram for Predicting Postoperative Overall Survival in Advanced Stage III-IV Colorectal Cancer Patients.

Most colorectal cancer (CRC) patients are at an advanced stage when they are first diagnosed. Risk factors for predicting overall survival (OS) in advanced stage CRC patients are crucial, and constructing a prognostic nomogram model is a scientific method for survival analysis. A total of 2956 advanced stage CRC patients were randomised into training and validation groups at a 7:3 ratio. Univariate and multivariate Cox proportional hazards regression analyses were used to screen risk factors for OS and subsequently construct a prognostic nomogram model for predicting 1-, 3-, 5-, 8- and 10-year OS of advanced stage CRC patients. The performance of the model was demonstrated by the area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Kaplan-Meier curves were used to plot the survival probabilities for different strata of each risk factor. There was no statistically significant difference (p > 0.05) in the 32 clinical variables between patients in the training and validation groups. Univariate and multivariate Cox proportional hazards regression analyses demonstrated that age, location, TNM, chemotherapy, liver metastasis, lung metastasis, MSH6, CEA, CA199, CA125 and CA724 were risk factors for OS. We estimated the AUC values for the nomogram model to predict 1-, 3-, 5-, 8- and 10-year OS, which in the training group were 0.826 (95% CI: 0.807-0.845), 0.836 (0.819-0.853), 0.839 (0.820-0.859), 0.835 (0.809-0.862) and 0.825 (0.779-0.870) respectively; in the validation group, the corresponding AUC values were 0.819 (0.786-0.852), 0.831 (0.804-0.858), 0.830 (0.799-0.861), 0.815 (0.774-0.857) and 0.802 (0.723-0.882) respectively. Finally, the 1-, 3-, 5-, 8- and 10-year OS rates for advanced stage CRC patients were 73.4 (71.8-75.0), 49.5 (47.8-51.4), 43.3 (41.5-45.2), 40.1 (38.1-41.9) and 38.6 (36.6-40.8) respectively. We constructed and validated an original nomogram for predicting the postoperative OS of advanced stage CRC patients, which can help facilitates physicians to accurately assess the individual survival of postoperative patients and identify high-risk patients.

Zn2+ enhanced the anti-breast cancer activity of fucoidan based nanoparticles by activating the cGAS-STING pathway

The incidence rate of breast cancer remains high, and lung metastasis often leads to treatment failure. Immunotherapy based on the cyclic guanosine monophosphate synthesis (cGAS) − interface gene stimulatory factor (STING) pathway is expected to bring benefits to the treatment of breast cancer. This study provided a delivery system based on fucoidan (Fu) and polyvinylpyrrolidone (PVP) for the potential molecule resveratrol (Res). The study confirmed that Fu and PVP were assembled into nanoparticles through hydrogen bonding and effectively loaded Res (Fu/PVP/Res). Interestingly, the adsorption of Zn2+ (Fu/PVP/Res Zn2+) was expected to provide impetus for the treatment of breast cancer. The results in vitro confirmed that Fu/PVP/Res Zn2+ significantly inhibited the proliferation of breast cancer 4T1 cells, induced the accumulation of mitochondrial reactive oxygen species (ROS) and the damage of mitochondrial membrane potential (MMP), and further induced the cytoplasmic release of mtDNA, which was the direct cause of the activation of cGAS-STING pathway. In vivo studies confirmed that Fu/PVP/Res Zn2+ treatment inhibited the growth of 4T1 transplanted tumors. Excitingly, Fu/PVP/Res Zn2+ treatment also prevented lung metastasis of in situ tumors. The in vivo mechanism confirmed that Fu/PVP/Res Zn2+ treatment activated the cGAS-STING pathway and induced abnormal expression of tumor apoptosis factors such as Bax/Bcl-2. In conclusion, our research provided potential for the treatment of breast cancer.

Inhibition of Notch enhances efficacy of immune checkpoint blockade in triple-negative breast cancer.

Aberrant Notch, which is a defining feature of triple-negative breast cancer (TNBC) cells, regulates intercellular communication in the tumor immune microenvironment (TIME). This includes tumor-associated macrophage (TAM) recruitment through Notch-dependent cytokine secretion, contributing to an immunosuppressive TIME. Despite the low response rate of TNBC to immune checkpoint blockade (ICB), here, we report that inhibition of Notch-driven cytokine-mediated programs reduces TAMs and induces responsiveness to sequentially delivered ICB. This is characterized by the emergence of GrB+ cytotoxic T lymphocytes (CTLs) in the primary tumor. A more impressive effect of sequential treatment is observed in the lung where TAM depletion and increased CTLs are accompanied by near-complete abolition of metastases. This is due to (i) therapeutic reduction in Notch-dependent, prometastatic circulating factors released by the primary tumor, and (ii) elevated PD ligand 1 (PD-L1) in lung metastases, rendering them profoundly sensitive to ICB. These findings highlight the potential of combination cytokine inhibition and ICB as an immunotherapeutic strategy in TNBC.

Stromal Tumor-Infiltrating Lymphocytes in Hormone Receptor–Positive/HER2 Negative Metastatic Breast Cancer

The immune landscape of hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer (HR+/HER2− mBC), the most common subtype of BC, remains understudied. This is mainly because of reduced sample acquisition opportunities from metastases as compared with primary tumors. In this study, we explored stromal tumor-infiltrating lymphocytes (sTIL) in metastatic samples collected through our postmortem tissue donation program UZ/KU Leuven Postmortem Tissue Donation program to Enhance Research (NCT04531696). sTIL were scored as a continuous parameter according to the international guidelines on 427 metastases and 38 primary untreated tumors acquired from 20 patients with HR+/HER2− mBC. Estrogen receptor (ER) status was evaluated on 362 metastases with a cutoff value for positivity set at 1% according to the American Society of Clinical Oncology/College of American Pathologists guidelines. Our analyses show that 54% and 15% of metastases had sTIL levels of ≥1% and ≥5%, respectively. sTIL levels tended to be lower in metastases as compared with their respective primary tumors (estimate, -2.83; 95% CI, -5.77 to 0.11; P = .07). sTIL levels were lower in metastases from invasive lobular carcinoma than in metastases from invasive breast carcinoma of no special type (estimate, -1.67; 95% CI, -2.35 to -0.98; P < .001). A loss of ER expression was observed in 14% of all metastases, yet a negative ER status was not significantly associated with increased sTIL levels. Finally, sTIL levels were significantly higher in lung and axillary lymph node metastases compared with all metastases. Although these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provide novel and valuable insights into the state of immune infiltration in patients with HR+/HER2− mBC.

EZH2 Promotes Glioma Cell Proliferation, Invasion, and Migration via Mir-142-3p/KCNQ1OT1/HMGB3 Axis : Running Title: EZH2 Promotes Glioma cell Malignant Behaviors.

This study investigates the role and molecular mechanism of EZH2 in glioma cell proliferation, invasion, and migration. EZH2, miR-142-3p, lncRNA KCNQ1OT1, LIN28B, and HMGB3 expressions in glioma tissues and cells were determined using qRT-PCR or Western blot, followed by CCK-8 assay detection of cell viability, Transwell detection of invasion and migration, ChIP analysis of the enrichment of EZH2 and H3K27me3 on miR-142-3p promoter, dual-luciferase reporter assay and RIP validation of the binding of miR-142-3p-KCNQ1OT1 and KCNQ1OT1-LIN28B, and actinomycin D detection of KCNQ1OT1 and HMGB3 mRNA stability. A nude mouse xenograft model and a lung metastasis model were established. EZH2, KCNQ1OT1, LIN28B, and HMGB3 were highly expressed while miR-142-3p was poorly expressed in gliomas. EZH2 silencing restrained glioma cell proliferation, invasion, and migration. EZH2 repressed miR-142-3p expression by elevating the H3K27me3 level. miR-142-3p targeted KCNQ1OT1 expression, and KCNQ1OT1 bound to LIN28B to stabilize HMGB3 mRNA, thereby promoting its protein expression. EZH2 silencing depressed tumor growth and metastasis in nude mice via the miR-142-3p/KCNQ1OT1/HMGB3 axis. In conclusion, EZH2 curbed miR-142-3p expression, thereby relieving the inhibition of KCNQ1OT1 expression by miR-142-3p, enhancing the binding of KCNQ1OT1 to LIN28B, elevating HMGB3 expression, and ultimately accelerating glioma cell proliferation, invasion, and migration.

Development and validation of machine learning models for predicting lung metastasis risk in differentiated thyroid cancer based on two databases

Development and validation of machine learning models for predicting lung metastasis risk in differentiated thyroid cancer based on two databases

Reduced lung metastasis in endothelial cell-specific TGF-β type II receptor-deficient mice with decreased CD44 expression

Reduced lung metastasis in endothelial cell-specific TGF-β type II receptor-deficient mice with decreased CD44 expression