Renal cell carcinoma (RCC) is notorious for its propensity to metastasize even after a prolonged period of remission following nephrectomy. The metastatic spread can occur months or even years after initial treatment, which necessitates a heightened level of clinical awareness and vigilance in patients with a history of renal malignancy, particularly who present with new or unexplained nasal symptoms. Although RCC most commonly metastasize to the lungs, bones and liver, its involvement in the nasal cavity is exceedingly rare, posing significant diagnostic challenges due to the non-specific nature of symptoms. We describe a case of metastatic renal cell clear cell carcinoma presenting with recurrent epistaxis and unilateral nasal obstruction. Immunohistochemistry studies play a crucial role in confirming the diagnosis and ruling out potential differential diagnoses, along with a comprehensive clinical history of the patient.

BACKGROUND

Primary cancers of the appendix are rare, with an incidence of approximately 1.2 cases per 100,000 people per year and this tumor is difficult to diagnose preoperatively. The purpose of this paper is to present a rare case of metastatic mucinous carcinoma of the appendix and to provide a high index of suspicion to patients presenting with the same history, signs, and symptoms.

We present a case of a 33-year-old Filipina who reported abdominal pain and right lower quadrant mass. Following several preoperative diagnostic tests, a colonoscopy revealed synchronous tumors in various locations, prompting the need for an exploratory laparotomy to evaluate the abdomen. Histopathological examination was performed to confirm the final diagnosis which revealed primary mucinous carcinoma of the appendix. The tumor had extended into adjacent structures, including the cecal colon, ileum, and right ureter. Metastatic lesions were also identified in the descending and sigmoid colon. The disease was classified as stage IVC (T4b, N1c, M1c), indicating advanced progression with both extensive local invasion and distant metastasis.

Histopathology remains the gold standard for cancer diagnosis. Given the rarity and complexity of appendiceal mucinous carcinoma, a multidisciplinary approach is also essential. This collaborative strategy from various specialties is vital not only for achieving an accurate diagnosis but also for developing and implementing an effective, individualized treatment plan that addresses the distinct challenges of this uncommon malignancy.

Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
Epithelial-Mesenchymal Transition/drug effects* ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Humans ; Animals ; Lung Neoplasms/metabolism* ; Chemokines, CC/antagonists & inhibitors* ; Mice ; Mice, Nude ; Drugs, Chinese Herbal/administration & dosage* ; Cell Line, Tumor ; Neoplasm Metastasis ; Tumor-Associated Macrophages/drug effects* ; Mice, Inbred BALB C ; Signal Transduction/drug effects*

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics* ; Wnt Signaling Pathway/drug effects* ; Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neoplasm Metastasis/prevention & control* ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Neutrophil Infiltration/drug effects* ; Down-Regulation/drug effects* ; Cell Movement/drug effects* ; beta Catenin/genetics* ; Apoptosis/drug effects* ; Mice, Inbred C57BL ; Male ; Neoplastic Cells, Circulating/drug effects*

OBJECTIVES: This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC. METHODS: The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model. RESULTS: LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor. CONCLUSIONS LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Animals ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness ; Cell Proliferation ; Mice, Nude ; Cell Movement ; Lysosomal Membrane Proteins/genetics* ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Objective To elucidate the molecular mechanism by which exosomes (Exo) derived from cancer-associated fibroblasts (CAF) carrying HOX transcript antisense intergenic RNA (lncRNA HOTAIR) promote the metastasis of esophageal squamous cell carcinoma (ESCC). Methods CAFs were collected from tumor tissues, and non-cancer associated fibroblasts (NFs) were obtained from adjacent normal tissues at least 5 cm away from the tumor. Exosomes (CAFs-Exo and NFs-Exo) were isolated from conditioned media collected from CAFs or NFs. CAFs-Exo and NFs-Exo were incubated with human ESCC cell line TE-1 for 24 hours, and CCK-8 was used to determine the cell proliferation ability. Scratch test and Transwell test were performed to determine the cell migration and invasion ability. TE-1 cells were divided into the following two groups: NC group and KD group. The NC group and KD group were transfected with control siRNAs or siRNAs targeting HOTAIR respectively. The effects of HOTAIR knock-down on cell proliferation, migration, invasion and glycolysis were determined. Results CAFs-Exo promoted the proliferation of TE-1 cells more significantly than NFs-Exo. Compared with NFs-Exo group, the migration and invasion ability of TE-1 cells treated with CAFs-Exo were improved significantly. In addition, CAFs-Exo treatment inhibited the expression of E-cadherin and enhanced the expression of N-cadherin. The expression of HOTAIR in CAFs was significantly higher than that in NFs. Compared with NFs-Exo, the expression level of HOTAIR in CAFs-Exo increased significantly. Compared with NC group, the proliferation, migration and invasion of TE-1 cells in KD group decreased significantly. Compared with NC group, hexokinase 2 (HK2), extracellular acidification rate (ECAR) and ATP/ADP ratio of TE-1 cells in KD group decreased significantly. Conclusion HOTAIR, an exosome derived from CAFs, may be involved in metastasis and EMT by regulating glycolysis in ESCC cells.
Humans ; RNA, Long Noncoding/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Esophageal Squamous Cell Carcinoma ; Exosomes/genetics* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Glycolysis/genetics* ; Cancer-Associated Fibroblasts/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Cadherins/genetics*

Objective To investigate whether PLCB1 expression leads to gastric adenocarcinoma metastasis and poor prognosis, and to preliminarily analyze its mechanism. Methods 122 gastric adenocarcinoma patients and their adjacent non-cancerous tissues were selected, and tissue microarray technology was used to detect the expression levels of PLCB1, epithelial cadherin(E-cadherin), vimentin and CD8⁺ T cells by immunohistochemistry, and scored by two pathologists. According to the immunohistochemical score of PLCB1, the patients were divided into PLCB1 high expression group (IHC>90) and PLCB1 low expression group (IHC≤90). The clinical pathological characteristics, epithelial mesenchymal transition(EMT)-related proteins and CD8⁺ T cells expression differences between the two groups were compared. The overall survival of the patients was collected, and COX regression analysis and Kaplan-Meier curve were used to evaluate the relationship between PLCB1 expression level and prognosis. Results PLCB1 was highly expressed in 55 cases of gastric adenocarcinoma tissues, while only 12 cases in adjacent non-cancerous tissues. The tumor invasion depth, lymph node metastasis degree and TNM stage of the PLCB1 high expression group were higher than those of the PLCB1 low expression group. Chi-square test showed that PLCB1 expression level was negatively correlated with E-cadherin (r=-0.339), positively correlated with vimentin (r=0.211), and negatively correlated with CD8⁺ T cells (r=-0.343). Kaplan-Meier curve analysis showed that the overall survival and disease-free survival of gastric adenocarcinoma patients with high PLCB1 expression were significantly reduced. Multivariate COX regression analysis showed that except for lymph node metastasis, tumor invasion depth, TNM stage, E-cadherin and vimentin were also independent prognostic factors for gastric adenocarcinoma patients. Conclusion PLCB1 is highly expressed in gastric adenocarcinoma, and is closely related to tumor aggressiveness and prognosis. PLCB1 may induce EMT and inhibit CD8⁺ T cell infiltration to affect gastric adenocarcinoma metastasis and immune response.
Humans ; Stomach Neoplasms/genetics* ; Epithelial-Mesenchymal Transition ; Male ; Female ; Middle Aged ; Prognosis ; Adenocarcinoma/genetics* ; Cadherins/metabolism* ; Aged ; Adult ; CD8-Positive T-Lymphocytes/immunology* ; Vimentin/metabolism* ; Lymphatic Metastasis ; Neoplasm Metastasis

OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

Patients with metastatic castration-resistant prostate cancer (mCRPC) face poor prognoses due to tumor heterogeneity and drug resistance. Antibody-drug conjugates (ADCs) have been under development for over two decades for mCRPC treatment. Several clinical trials have demonstrated promising antitumor activity and acceptable safety profiles for ADCs in this setting. Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 and DXC008 (both dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC has been initiated in May 2025 for evaluating B7-H3-targeted ADC ifinatamab deruxtecan. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of mCRPC.
Humans ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Male ; Immunoconjugates/therapeutic use* ; Glutamate Carboxypeptidase II/immunology* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; B7 Antigens/immunology* ; Neoplasm Metastasis ; Prostate-Specific Antigen ; Antigens, Neoplasm/immunology* ; Antigens, Surface ; Camptothecin/analogs & derivatives* ; Oxidoreductases