Metastatic Research Articles

Small cell lung cancer with peripheral neuropathy as the first symptom: Two case reports

BACKGROUND Small cell lung cancer (SCLC) is the most malignant type of lung cancer. Even in the latent period and early stage of the tumor, SCLC is prone to produce distant metastases with complex and diverse clinical manifestations. SCLC is most closely related to paraneoplastic syndrome, and some cases present as paraneoplastic peripheral neuropathy (PPN). PPN in SCLC appears early, lacks specificity, and often occurs before diagnosis of the primary tumor. It is easy to be misdiagnosed as a primary disease of the nervous system, leading to missed diagnosis and delayed diagnosis and treatment. CASE SUMMARY This paper reports two cases of SCLC with limb weakness as the first symptom. The first symptoms of one patient were rash, limb weakness, and abnormal electromyography. The patient was repeatedly referred to the hospital for limb weakness and rash for > 1 year, during which time, treatment with hormones and immunosuppressants did not lead to significant improvement, and the condition gradually aggravated. The patient was later diagnosed with SCLC, and the dyskinesia did not worsen as the dermatomyositis improved after antineoplastic and hormone therapy. The second case presented with limb numbness and weakness as the first symptom, but the patient did not pay attention to it. Later, the patient was diagnosed with SCLC after facial edema caused by tumor thrombus invading the vein. However, he was diagnosed with extensive SCLC and died 1 year after diagnosis. CONCLUSION The two cases had PPN and abnormal electromyography, highlighting its correlation with early clinical indicators of SCLC.

Associations Between Problem List Items and Clinically Significant Distress in Patients with Metastatic Spine Disease.

Retrospective cohort study. This study aimed to identify sources of distress in patients with metastatic spine disease and elucidate factors associated with clinically significant distress. Distress is associated with poorer outcomes and lower quality of life in cancer patients. Patients with metastatic spine disease are particularly vulnerable to clinically significant levels of distress. However, specific factors contributing to distress in these patients have been largely unexplored. We retrospectively reviewed medical records of patients with metastatic spine disease (MSD) who underwent surgery from 2015 to 2023. We analyzed National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) scores and Problem List items within 30 days prior to surgery, which was defined as "baseline" distress. We calculated the frequency of each problem and the proportion of patients with clinically significant distress (DT score ≥4). We used chi-square tests to analyze associations between Problem List items and significant distress, with a significance threshold of P<0.05. Among 160 patients with MSD, 48.1% reported clinically significant distress. Patients most frequently reported Physical concerns (93.8%), followed by Emotional (55.6%) and Practical concerns (31.9%). The most common individual Problem List item was pain (72.5%), followed by fatigue (48.1%) and worry (41.2%). Emotional (P=0.001), Practical (P=0.04), and Social concerns (P=0.039) were significantly associated with clinically significant distress, but Physical concerns were not (P=0.05). Though physical concerns were most common for patients with MSD, emotional and practical concerns were more strongly associated with significant distress among patients with metastatic spine disease. These findings highlight the need for multidisciplinary care focused on emotional and practical issues to enhance patients' quality of life.

Treatment intensification in metastatic castration-sensitive prostate cancer: a real-world study in Alberta, Canada.

To assess the current status of and factors associated with treatment intensification (TI) (with androgen receptor pathway inhibitors [ARPIs] and/or docetaxel) for metastatic castration-sensitive prostate cancer (mCSPC) in Canada. Retrospective analysis of data for 431 patients with mCSPC from the Alberta Prostate Cancer Research Initiative database (July 2014-March 2022). The primary objective was to assess the patient proportion receiving TI, time to TI, and associated factors. The secondary and exploratory objectives were evaluating TI patterns and factors associated with choice of therapy, respectively. Overall, 42% of patients received TI; most (65%) within 3 months post-index. TI was likely to occur within 3 months post-index in de novo mCSPC, but occurred later for recurrent mCSPC. Patients with recurrent mCSPC (HR [95% CI]: 0.52 [0.38-0.72]) and those aged ≥ 75 years (0.57 [0.36-0.93]) were less likely to receive TI. Patients with multiple metastatic sites and bone metastasis had a 2-3-fold higher likelihood of receiving TI. An ARPI was predominantly used (75%) for TI (median duration: 16.0 months). TI rates for mCSPC are suboptimal in Canada especially for older patients and those with recurrent mCSPC. TI prioritization in such groups may improve patient outcomes.

Treatment decision-making and treatment experiences in men with metastatic castration-resistant prostate cancer.

For the most advanced stage of metastatic castration-resistant prostate cancer (mCRPC), several life-prolonging treatments have become available over the past decade. Treatment decision-making (TDM) and experiences in this phase are yet to be studied. Hence, this study aimed to describe men's satisfaction with TDM and treatment experiences during the first 12 months of a life-prolonging treatment of mCRPC. This prospective study included 104 men with mCRPC who started and remained on the same life-prolonging treatment for 12 months. They received a questionnaire on TDM, treatment experiences, and well-being every 3 months. Correlation analyses explored associations between satisfaction with TDM at baseline and treatment experiences and well-being over time. The participants (median age: 77 years) generally reported high satisfaction with physician- and nurse communication and confidence/trust at baseline (>55% reported the highest satisfaction in all questions), but lower satisfaction with communication regarding how the treatments could affect them - up to 40% reported not having talked about that at all. Treatment experiences and physical- and emotional well-being remained stable over time. Associations were found between satisfaction with TDM at baseline and how they rated the treatment as a whole at six months, and well-being at six and 12 months. In mCRPC, men's TDM preferences need to be explored, and shared decision-making needs to be facilitated when considering treatment. Furthermore, clinicians need to discuss how the treatment might affect patients' everyday lives when discussing life-prolonging treatments with them.

Predictive model using systemic inflammation markers to assess neoadjuvant chemotherapy efficacy in breast cancer

BackgroundPathological complete response (pCR) is an important indicator for evaluating the efficacy of neoadjuvant chemotherapy (NAC) in breast cancer. The role of systemic inflammation markers in predicting pCR and the long-term prognosis of breast cancer patients undergoing NAC remains controversial. The purpose of this study was to explore the potential predictive and prognostic value of systemic inflammation markers (NLR, PLR, LMR, NMR) and clinicopathological characteristics in breast cancer patients receiving NAC and construct a pCR prediction model based on these indicators.MethodsA retrospective analysis was conducted on 209 breast cancer patients who received NAC at Nanjing Drum Tower Hospital between January 2010 and March 2020. Independent sample t-tests, chi-square tests, and logistic regression models were used to evaluate the correlation between clinicopathological data, systemic inflammation markers, and pCR. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cut-off values for NLR, PLR, and LMR. Survival analysis was performed using the Kaplan-Meier method and log-rank test. A predictive model for pCR was constructed using machine learning algorithms.ResultsAmong the 209 breast cancer patients, 29 achieved pCR. During a median follow-up of 68 months, 74 patients experienced local or distant metastasis, and 56 patients died. Univariate logistic regression analysis showed that lymph node status, HER-2 status, NLR, PLR, and LMR were associated with pCR. ROC curve analysis revealed that the optimal cut-off values for NLR, PLR, and LMR were 1.525, 113.620, and 6.225, respectively. Multivariate logistic regression analysis indicated that lymph node status, NLR, and LMR were independent predictive factors for pCR. Survival analysis demonstrated that lymph node status, NLR, and LMR were associated with prognosis. Machine learning algorithm analysis identified the random forest (RF) model as the optimal predictive model for pCR.ConclusionThis study demonstrated that lymph node status, NLR, and LMR had significant value in predicting pCR and prognosis in breast cancer patients. The RF model provides a simple and cost-effective tool for pCR prediction, offering strong support for clinical decision-making in breast cancer treatment and aiding in the optimization of individualized treatment strategies.

Membrane-Anchoring and Oxygen-Generating Mediated Nanosonosensitizer for Optimizing Cancer Immunotherapy.

Despite its antitumor promise, sonodynamic therapy (SDT)'s efficacy in immune activation requires enhancement, primarily due to the hypoxic tumor microenvironment (TME) and insufficient targeting of sonosensitizers to specific subcellular regions. Herein, we developed macrophage membrane (MM)-intermingled membrane fusogenic liposomes (MFL) to optimize sonoimmunotherapy that encapsulate catalase (CAT) within the core and incorporate the sonosensitizer chlorin e6 (Ce6) in the outer shell (CAT@MM-MFL-Ce6). The MM confers immune evasion properties and promotes nanoparticles' targeted accumulation in tumor tissue. The membrane fusion effect enables Ce6 to anchor onto cancer cell membrane and facilitates the direct delivery of CAT into the cytoplasm, bypassing endosomal degradation. Upon ultrasound stimulation, generated reactive oxygen species directly damage the plasma membrane, initiating the Caspase 3/Gasdermin E-mediated pyroptosis pathway. Concurrently, the encapsulated CAT efficiently decompose H₂O₂ in the cytoplasm, thus enhancing local oxygen levels in hypoxic tumors. Contributed by these effects, the combination of nanosonosensitizer-augmented SDT and immune checkpoint agent successfully reverse the immunosuppressive TME, driving a potent immune response that inhibits primary tumor growth, distant metastasis, and lung metastases in an orthotopic triple-negative breast cancer model. This study demonstrates the potential of a novel SDT-based combinatorial approach to modulate immune-cold TMEs, advancing proof-of-concept tumor therapeutics.

Approach to the Management of Gastrointestinal Manifestations in Patients With Phaeochromocytoma and Paraganglioma.

Managing gastrointestinal symptoms in patients with phaeochromocytoma and paraganglioma (PPGL) is challenging due to the risk of catecholaminergic crisis with many commonly prescribed medications, especially in functional tumours. We reviewed gastrointestinal symptom management and outcomes in PPGL patients at our centre and developed recommendations based on a literature review and our experience. A single-centre retrospective analysis of the management of gastrointestinal symptoms in patients with PPGL between 2019 and 2024 was completed. A literature review of gastrointestinal manifestations in PPGL was undertaken. Twenty-four individuals with PPGL admitted for radionuclide therapy, chemotherapy, surgery or other medical illness were included. Eighteen (75%) had metastatic disease. Fifty administration events of antiemetics for nausea or vomiting occurred. Two patients had acute colonic pseudo-obstruction. Dopamine antagonists (metoclopramide) and corticosteroids (dexamethasone) were administered to 10 and 9 patients, respectively, the majority of whom were alpha-blocked (n = 7) or had a dopaminergic/biochemically silent phenotype (n = 10). A patient with noradrenergic PPGL experienced a hypertensive episode following high-dose dexamethasone. No patients with biochemically negative/dopaminergic phenotypes or on alpha blockade experienced an antiemetic-related adverse event. Published evidence of dopamine antagonists and corticosteroids precipitating catecholaminergic crisis was mostly limited to case reports. While low-risk antiemetics (serotonin, histamine or neurokinin antagonists) are preferable, we found higher-risk antiemetics (dexamethasone and metoclopramide) can be cautiously administered in patients with a biochemically negative/dopaminergic phenotype or in those on adequate alpha blockade. Limited case reports demonstrated anti-cholinergic agents were beneficial for the management of acute colonic pseudo-obstruction. Optimal management of gastrointestinal symptoms in PPGL should consider disease characteristics such as primary location, secretory profile, alpha blockade and medication profile.

Combination of MLo-1508 with sunitinib for the experimental treatment of papillary renal cell carcinoma

Renal cell carcinoma (RCC) is the 14th most incident cancer worldwide, and no curative therapeutic options are available for advanced and metastatic disease. Hence, new treatment alternatives are urgently needed to tackle disease management and drug resistance. Herein, we explored the use of MLo-1508 as an anti-tumoral agent in RCC and further assessed its combination with sunitinib for the treatment of papillary RCC. For that, different RCC cell lines were treated with both drugs, alone or in combination, and different phenotypic assays were performed. Moreover, global DNA methylation levels and specific DNMT3a activity were measured, and gene-specific CpG methylation and transcript levels were quantified after treatment. Finally, the combinatory potential of MLo-1508 and sunitinib were asses both in vitro and in vivo using the ACHN cell line. We found that MLo-1508 significantly decreased RCC cell viability while inducing apoptosis in a dose-dependent manner without cytotoxicity for non-malignant cells. Moreover, the treatment induced morphometric alterations and DNA damage in all RCC cell lines. MLo-1508 decreased DNMT1 and DNMT3A transcript levels in 786-O and ACHN cells, inhibited DNMT3A activity, and reduced the global DNA methylation content of ACHN cells. When combined with sunitinib, a reduction in ACHN cell viability, as well as cell cycle arrest at G2/M was observed. Importantly, MLo-1508 decreased the sunitinib effective anti-tumoral concentration against ACHN cell viability. In an in vivo ACHN CAM model, the combination induced cell necrosis. Thus, MLo-1508 might improve sensitivity to sunitinib treatment by decreasing the required concentration and delaying resistance acquisition.

Estrogen-induced FXR1 promotes endocrine resistance and bone metastasis in breast cancer via BCL2 and GPX4

Estrogen signaling dysregulation plays a critical role in the development of anti-estrogen resistance and bone metastasis of ER+ mammary carcinoma. Using quantitative proteomic screening, we identified FXR1 as an estrogen-regulated RNA-binding protein associated with anti-estrogen resistance. Mechanistically, estrogen and IGF1 facilitate FXR1 protein translation via the PI3K/AKT/mTOR/EIF4E pathway. FXR1 enhances cellular resistance to apoptosis and ferroptosis by facilitating the maturation of BCL2 pre-mRNA and stabilizing GPX4 mRNA, respectively. Anti-estrogen resistant cells exhibit elevated FXR1 expression, and FXR1 depletion restores their sensitivity to tamoxifen. Moreover, combining FXR1 depletion with a ferroptosis inducer induces synergistic lethal in anti-estrogen resistant cells. Finally, we provide proof-of-concept evidence supporting FXR1 antagonism as a potential treatment for bone metastases in ER+ breast cancer. Our findings highlight FXR1 as a promising therapeutic target to improve existing therapeutic regimes for ER+ breast cancer patients.

Predicting preoperative lymph node metastasis in esophageal cancer: Advancement and challenges.

Accurate preoperative prediction of lymph node metastasis is crucial for developing clinical management strategies for patients with esophageal cancer. In this letter, we present our insights and opinions on a new nomogram proposed by Xu et al. Although this research has great potential, there are still concerns regarding the small sample size, limited consideration of biological complexity, subjective image segmentation, incomplete image feature extraction and statistical analyses. Furthermore, we discuss how to achieve more robust and accurate predictive performance in future research.

Endoscopy capabilities in diagnostics of intramural lymphogenous metastasis in esophageal cancer and esophagogastric junction cancer

The purpose of this article is to demonstrate the experience of the Astrakhan Regional Clinical Oncology Dispensary in diagnosing intramural metastasis of tumors of the esophagus and prostomial parts of the stomach, as well as to emphasize the importance of correctly assessing the extent of tumor damage to determine further treatment tactics. Materials and methods. 630 endoscopic examinations were performed on 570 patients with malignant tumors of the esophagus and proximal parts of the stomach with transition to the area of the esophagogastric junction and esophagus (ICD-O-3 C15.0, 3-5, C 16.0) Results. The endoscopic picture of intramural metastases is diverse, but most often they were multiple or single elevated or flat-elevated neoplasms with a submucosal location, a predominant size of 3-5 mm, mainly with clear contours, grayish-pink or grayish-yellow color, dense consistency. Conclusion. Detection of intramural metastases affects the determination of disease staging and, accordingly, the development of treatment strategy.

Relationship Between Tumor Infiltrating Lymphocytes (TIL) With Histopathological Grading, Tumor Size, and Axillary Lymph Node Metastases in Breast Cancer at the Anatomical Pathology Laboratory of Soedarso Hospital Pontianak

Relationship Between Tumor Infiltrating Lymphocytes (TIL) With Histopathological Grading, Tumor Size, and Axillary Lymph Node Metastases in Breast Cancer at the Anatomical Pathology Laboratory of Soedarso Hospital Pontianak

Comparable impact of lymph node metastases in T2 gallbladder cancer on postoperative prognosis irrespective of the extent of the metastases: A retrospective analysis.

Lymph node metastases beyond the hepatoduodenal ligament are sometimes encountered in locally limited T2 gallbladder cancer (GBCA). However, the incidence and impact on prognosis remain unclear. This was a retrospective multi-institutional study of patients who underwent surgical resection for GBCA from 2002 to 2022. The eighth edition of the Union for International Cancer Control staging was used for tumor-node-metastasis categorization. The lymph node location was classified as follows: (A) along the hepatoduodenal ligament and common hepatic artery; (B) posterior side of the pancreatic head; and (C) others. Metastasis to regions A, B, and C nodes was denoted as Na, Nb, and Nc, respectively. Data for 379 patients (pT1, 29; pT2, 162: pT3, 141; and pT4, 47) were evaluated; none with pT1 GBCA had node metastasis. For N1/2 GBCA, the proportion of patients with N2 disease increased with increasing T grade (p = .001), while the proportions of patients with Na, Nb, and Nc disease were comparable between pT2 (61%, 26%, and 13%), pT3 (63%, 26%, and 12%), and pT4 (50%, 38%, and 12%) disease (p = .681), respectively. Overall survival for pT2N1/2 disease (5 years, 43.8%) was comparable to that for pT3/4N0 disease (5 years, 37.2%; p = .192). Among patients with node-positive pT2 disease, overall survival was comparable for Na, Nb, and Nc disease, with 5-year survivals of 46%, 43%, and 31%, respectively (p = .346). Region B or C node metastasis was not rare even in pT2 GBCA. Regarding survival outcomes, pT2 node-positive GBCA should be considered advanced disease irrespective of the extent of node metastasis.

Near-Infrared Light-Responsive Immunomodulator Prodrugs Rejuvenating Immune Microenvironment for "Cold" Tumor Photoimmunotherapy.

Light-activatable prodrugs have been applied in precision cancer therapy because of their spatiotemporal controllability and minimal toxic side effects. However, the reported prodrugs were limited by the ultraviolet and visible light regions, which seriously restricted their application in deep tissues. Developing a near-infrared (NIR) light-activatable release system remains a great challenge. Herein, the 808 nm light-activatable prodrugs were constructed with imiquimod (R837) and NIR boron dipyrromethene (BODIPY) via a reactive oxygen species (ROS)-cleavable linker for photoimmunotherapy of "cold" cancer. ROS produced by BODIPY could cleave the linker under 808 nm laser irradiation, and R837 was released spatiotemporally at the tumor site. The combination of the immune response produced by R837 and immunogenic cell death caused by phototherapy significantly potentiated adaptive antitumor immunity and enhanced cytotoxic CD8+ T cell infiltration for tumor metastasis and distant tumor inhibition. This work provides an effective NIR light-activatable controlled release system for cancer immunotherapy and metastasis suppression.

Hematological toxicity of [225Ac]Ac-PSMA-617 and [177Lu]Lu-PSMA-617 in RM1-PGLS syngeneic mouse model

BackgroundProstate cancer (PC) has a 34% 5-year survival rate after progressing to metastatic castration-resistant prostate cancer (mCRPC), which occurs in 20–30% of cases. Treatments like chemotherapy, immunotherapy, and PSMA-targeted radioligand therapy (RLT) show promise, but challenges remain with tumor resistance, side effects, and dose-limiting toxicity in kidneys and bone marrow. This study investigated the hematotoxicity, treatment efficacy, and recovery after [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 treatment in a syngeneic PC mouse model.MethodTwenty-five male C57BL/6 mice were inoculated with RM1-PGLS cells and monitored using [68Ga]Ga-PSMA-11 PET/CT. The mice were divided into five groups as follows: (1) [225Ac]Ac-PSMA-617 treatment with tumors, (2) [177Lu]Lu-PSMA-617 treatment with tumors, (3) control group with tumors, (4) [225Ac]Ac-PSMA-617 treatment without tumors, and (5) [177Lu]Lu-PSMA-617 treatment without tumors. Tumor volume was measured weekly, and animals were sacrificed when tumors reached 1.5 cm³. Endpoint criteria included tumor size, survival, and body mass. Blood samples were collected at different time points to assess blood cell counts and liver and kidney function.ResultsBoth treatments significantly slowed tumor progression and extended survival. [225Ac]Ac-PSMA-617-treated mice had a median survival of 70 days, compared to 58 days for [177Lu]Lu-PSMA-617-treated mice and 30 days for the control group. Tumor volumes were significantly reduced in both treatment groups (P < 0.05). Hematological analysis showed that both treatments reduced WBCs, RBCs, and platelets, but values normalized within 35–42 days. Liver and kidney functions remained unaffected, and no significant renal or hepatic toxicity was observed.ConclusionBoth [225Ac]Ac-PSMA-617 and [177Lu]Lu-PSMA-617 caused transient hematotoxicity without prolonged effects. The data do not explicitly support the necessity of immunocompetent models for studying therapeutic outcomes in this context. Future studies incorporating immune profiling are warranted to investigate immune system interactions in radioligand therapy further.

Promising outcomes of the PD-L1 inhibitor Socazolimab in recurrent and metastatic cervical cancer: a case report

Promising outcomes of the PD-L1 inhibitor Socazolimab in recurrent and metastatic cervical cancer: a case report

Blood-based detection of MMP11 as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-β1 signaling mechanism

BackgroundProstate cancer (PCa) is the second most common type of tumor diagnosed in men and the fifth leading cause of cancer-related death in male patients. The response of metastatic disease to standard treatment is heterogeneous. As for now, there is no curative treatment option available for metastatic PCa, and the clinical tests capable of predicting metastatic dissemination and metastatic response to the therapies are lacking. Our recent study identified aldehyde dehydrogenases ALDH1A1 and ALDH1A3 as critical regulators of PCa metastases. Still, the exact mechanisms mediating the role of these proteins in PCa metastatic dissemination remain not fully understood, and plasma-based biomarkers of these metastatic mechanisms are not available.MethodsGenetic silencing, gene overexpression, or treatment with different concentrations of the retinoic acid (RA) isomers, which are the products of ALDH catalytic activity, were used to modulate the interplay between retinoic acid receptors (RARs) and androgen receptor (AR). RNA sequencing (RNAseq), reporter gene assays, and chromatin immunoprecipitation (ChIP) analysis were employed to validate the role of RARs and AR in the regulation of the transforming growth factor-beta 1 (TGFB1) expression. Gene expression levels of ALDH1A1, ALDH1A3, and the matrix metalloproteinase 11 (MMP11) and their correlation with pathological parameters and clinical outcomes were analysed by mining several publicly available patient datasets as well as our multi-center transcriptomic dataset from patients with high-risk and locally advanced PCa. The level of MMP11 protein was analysed by enzyme-linked immunosorbent assay (ELISA) in independent cohorts of plasma samples from patients with primary or metastatic PCa and healthy donors, while plasma proteome profiles were obtained for selected subsets of PCa patients.ResultsWe could show that ALDH1A1 and ALDH1A3 genes differently regulate TGFB1 expression in a RAR- and AR-dependent manner. We further observed that the TGF-β1 pathway contributes to the regulation of the MMPs, including MMP11. We have confirmed the relevance of MMP11 as a promising clinical marker for PCa using several independent gene expression datasets. Further, we have validated plasma MMP11 level as a prognostic biomarker in patients with metastatic PCa. Finally, we proposed a hypothetical ALDH1A1/MMP11-related plasma proteome-based prognostic signature.ConclusionsTGFB1/MMP11 signaling contributes to the ALDH1A1-driven PCa metastases. MMP11 is a promising blood-based biomarker of PCa progression.

Aging potentially reduces CD169 expression in sinus macrophages of pelvic lymph nodes.

The number of patients with prostate cancer has been increasing around the world. Although anticancer immunotherapy targeting the immune checkpoint molecules has been approved for many types of cancer, no significant anti-cancer effects have been observed in patients with prostate cancer. Lymph node sinus macrophages (LSMs) are known to work as antigen-presenting cells, which are critical for anticancer immune responses. Previous studies have suggested that CD169 expression in LSMs affects anticancer immune responses in several cancers, including prostate cancer. In the present study, we aimed to examine the correlation between the tumor immune microenvironment and activation status of LSMs in patients with prostate cancer. Forty-two cases of high-risk localized prostate cancer treated using robot-assisted laparoscopic radical prostatectomy and lymph node dissection between 2017 and 2021 were enrolled. CD169 expression in LSMs was examined by immunohistochemistry. The results indicated that CD169 expression in LSMs was significantly decreased in older (≥ 75years) compared with younger patients. However, no significant correlation was found between CD169 expression and any other clinicopathological factors. In addition, CD3- and CD8-postitive lymphocytes in primary cancer tissues were evaluated in the same cases, and their correlations with CD169 expression in LSMs were tested. Although these lymphocytes tended to be higher in CD169high than in CD169low cases, the difference was not statistically significant. In conclusion, we found that CD169 expression was upregulated in older patients and tended to be related to T cell infiltration in cancer tissues. Therefore, the downregulation of CD169 in LSMs might be involved in the reduced anticancer immune response in prostate cancer.

The application of ANXA2 gene knockout mouse models in lung cancer metastasis

Objective: ANXA2 plays a crucial role in cancer metastasis, but its mechanism is not yet fully understood. Therefore, it is necessary to establish an ANXA2 gene knockout mouse model to provide an effective tool for subsequent studies on ANXA2-related mechanisms. Methods: A gene knockout mouse model was constructed using CRISPR/Cas9 technology. The model was validated through tissue DNA extraction followed by polymerase chain reaction (PCR), sequencing, and western blot to confirm ANXA2 genotype and protein expression. The successfully constructed models were divided into a model group and a wild-type (WT) group for the creation of a mouse tail vein injection Lewis lung carcinoma (LLC) metastasis model. Metastatic foci formation was monitored using in vivo imaging technology, and the survival rates of the two groups were compared. Results: An sgRNA sequence targeting the first exon of ANXA2 was designed, and 16 founder mice were obtained through microinjection. Through consanguineous hybridization, 30 homozygous offspring were ultimately acquired. After establishing the strains of the mouse model, mice were divided into the ANXA2 knockout group and the WT group, with 8 mice in each group. An LLC lung metastasis model was established in both groups. Compared with the WT group, the number of metastatic foci was significantly increased in the ANXA2 knockout group (7 vs. 1), and the fluorescence intensity was stronger in the WT group than in the knockout group (P=0.002). Using the GEPIA2 database to analyze ANXA2 gene expression in tumor tissues and normal tissues of lung cancer patients, it was found that ANXA2 expression levels were significantly higher in lung cancer tumor tissues compared to normal tissues (P＜0.05). The database included data from 478 lung cancer patients, and patients were stratified into high-expression and low-expression groups based on ANXA2 levels. Compared to the low-expression group, patients in the high-expression group exhibited significantly shorter disease-free survival and overall survival (P＜0.05, respectively). The survival time of mice in the ANXA2 knockout group (median survival time, 43 days) was significantly longer compared to the WT group (median survival time, 26 days; P=0.017). Additionally, ANXA2 expression is significantly associated with the prognosis of lung cancer patients (P=6.4e-14). Conclusions: ANXA2 is closely associated with cancer metastasis and holds potential as a new target for metastasis treatment. Further in-depth research will greatly facilitate the transition of ANXA2 from basic research to clinical application.

Biomimetic Cascade Nanozyme Catalytic System for the Treatment of Lymph Node Metastasis in Gastric Cancer.

Lymphatic metastasis of gastric cancer is a challenging issue in clinical practice. Recently, copper single-atom nanozymes (SAZ) have gained tremendous attention due to its superior peroxidase (POD) activity that has good nonocatalytic tumor therapy (NCT) capabilities, and photothermal properties. Therefore, using a high-expressing P-selectin platelet membrane (PM) to encapsulate SAZ and cisplatin is proposed, forming PSC nanoparticles. Due to their exquisite nanoscale size and the unique structure of lymphatic vessels, PSC can highly target cancer cells in invasive primary tumors and metastatic lymph nodes that both highly express CD44. It is noteworthy that cisplatin can simultaneously perform chemotherapy and generate H₂O₂ under the action of NADPH oxidases (NOXs) that further enhance the catalytic activity of SAZ and increase intracellular reactive oxygen species (ROS) production. Both in vitro and vivo experiments have demonstrated the superior targeting and elimination capability of the PCS system in primary and metastatic tumor cells. In addition, transcriptomic analysis reveals that PSC + NIR induced apoptosis in MFC cells. This marks the first proposal of combining single-atom nanozymes and chemotherapy drugs for dual-targeting in gastric cancer and lymphatic metastasis, providing new insights into a challenging clinical issue in the treatment of gastric cancer lymphatic metastasis.