Metastatic disease accounts for approximately 80% of cancer-related deaths, typically manifesting as single-organ failure mainly through abdominal, cardiovascular, neurological, or respiratory complications. Despite treating thousands of cancer patients daily worldwide, our understanding of organ-specific metastatic dissemination routes, tissue destruction mechanisms and reasons for organ failures remains limited. As cancer-directed therapies advance, maintaining organ function has emerged as a critical therapeutic goal of care. To develop more effective treatment strategies, a comprehensive understanding of the pathophysiology is essential, particularly regarding secondary and subsequent metastatic waves that lead to extensive macro-metastases and organ failure. Critical distinction between primary metastatic spread and secondary intra-organ dissemination is crucial. In the era of precision oncology, elucidating organ-specific destruction processes and the pathophysiology of metastatic waves is fundamental for advancing patient care. To highlight the emerging goal of care of maintaining organ function, we aligned the metastatic biology, clinical stages, goals of care and therapeutic indications: the Bio Therapeutic Goals of Cancer Care Model.

The organoid approach preserves the intricate molecular and genetic characteristics of tumor tissues, playing a pivotal role in advancing precision oncology. This preservation enables the exploration of cancer therapies and in vitro validation of drug efficacy. Organoids have emerged as indispensable tools in the study of urological cancers, facilitating research on tumorigenesis, drug testing, and the development of therapeutic combinations. Their superiority over traditional 2D cell cultures and patient-derived xenograft (PDX) models lies in their enhanced ability to more accurately replicate the in vivo environment. Modern organoid platforms integrate 3D bioprinting, co-culture systems, microfluidics, and artificial intelligence to significantly improve the precision, scalability, and efficiency of cancer research. These integrated systems serve as powerful analytical tools, propelling the development of personalized therapies for urological malignancies. This article provides a comprehensive review of the establishment and potential of organoid technologies in treating the three major urogenital system cancers-prostate, bladder, and renal-highlighting their trajectory from basic research to clinical applications and their expanding synergy with bioengineering innovations.

Ovarian small cell neuroendocrine carcinoma (OSCNEC) is rare and few cases have been reported, which makes preoperative diagnosis difficult. Moreover, no reports have yet described detailed imaging findings or findings of positron emission tomography with fluorine-18 fluorodeoxyglucose (¹⁸F-FDG-PET). Therefore, here we report a case of OSCNEC including detailed imaging findings and a literature review.

A 74-year-old woman with clinical symptoms of abdominal distension was referred to our hospital because of a pelvic mass detected by ultrasonography at another hospital. Serum levels of cancer antigen 125 and neuron-specific enolase (NSE) were both elevated, at 203.0 U/mL (normal range 0-35.0 U/ml) and 47.6 ng/ml (normal range 0-16.3 ng/ml), respectively. Magnetic resonance imaging at 3.0 Tesla showed a multilocular cystic tumor 18 cm in diameter in the pelvic cavity. The tumor had irregular septa and included a solid component. The cystic component showed partially high intensity suggesting hemorrhage on fat-suppressed T1WI. The solid component showed high intensity on diffusion-weighted imaging and contrast enhancement on contrast-enhanced fat-suppressed T1WI. Irregular peritoneal thickening and nodules suggesting peritoneal dissemination were also detected. ¹⁸F-FDG-PET/computed tomography (PET/CT) revealed high FDG uptake (maximum standardized uptake value: 13.0) in the solid component. Para-aortic lymph node, spinal, iliac, and liver metastases were detected along with peritoneal dissemination. Intertrabecular bone metastases were also clinically detected on PET/CT. Abdominal bilateral salpingo-oophorectomy, partial omentectomy, and appendectomy performed for surgical staging revealed the ovarian tumor was primary OSCNEC with peritoneal dissemination because no lung tumor was identified on PET/CT, which ruled out a metastatic ovarian tumor from small cell lung cancer. The patient received radiation therapy for vertebral metastases without chemotherapy and died four months after the operation.

OSCNEC could be considered when elevated serum NSE at diagnosis and hematogenic spread such as bone or liver metastases are found in a patient with a primary malignant ovarian tumor without a lung tumor on imaging, although MR findings of OSCNEC were not specific enough to differentiate it from other ovarian cancers.

Cancer is a deadly and fast-spreading disease that is a growing health problem worldwide due to a lack of comprehensive screening and appropriate medication. However, natural products derived from medicinal plants have gained attention as potential sources of bioactive compounds that selectively remove cancerous lesions and are nontoxic and safe. Pancreatic cancer (PC) is a major therapeutic challenge and is predicted to surpass breast cancer as the third leading cause of cancer death. This study investigated the cytotoxic effects of methanolic extracts from five Iranian medicinal plants, Cuscuta epithymum, Achillea millefolium, Salvia officinalis, Salvia hydrangea, and Teucrium polium, on pancreatic cancer cell lines (MIA PaCa-2 and PaTu8902). Additionally, we examined the changes in the expression of key genes following treatment with C. epithymum extract. The findings revealed that the plant extracts had a dose-dependent effect on the cell viability of the lines, with the C. epithymum extract exhibiting the greatest cytotoxic effect (IC50 values of 85.03 µg/mL for MIA PaCa-2 and 156.57 µg/mL for PaTu 8902). GC‒MS analysis revealed 25 bioactive compounds in C. epithymum, with quinic acid (14.13%), p-vinylphenol (13.22%), and valeraldehyde (11.21%) as the most abundant. The study also investigated the changes in the expression of the STAT4, PIK3CD, EMP1, and RAB11FIP3 genes in MIA PaCa-2 and PaTu 8902 pancreatic cancer cell lines after treatment with the extract from C. epithymum. A correlation was detected between the expression levels of PIK3CD, STAT4, EMP1, and RAB11FIP3 and various concentrations of C. epithymum extract. The results revealed that the extract increased the mRNA levels of STAT4, PIK3CD, and EMP1, whereas RAB11FIP3 was reduced in the treated cells. Accordingly, C. epithymum extract has strong cytotoxic effects on pancreatic cancer cells and influences the expression of key cancer-related genes, suggesting its potential as a therapeutic candidate for PC treatment. Further in vivo studies are recommended to explore its mechanisms of action and clinical applicability.

Long non-coding RNAs (lncRNAs) play essential roles in various physiological and pathological processes. Inferring new lncRNA-disease associations (LDAs) not only promotes us to better understand these complex biological processes, but also provides new options for the diagnosis and prevention of diseases.

A novel computational model, LDA-SCGB, is proposed to predict new LDAs. LDA-SCGB first extracts features of each lncRNA-disease pair with singular value decomposition. Next, it classifies unknown lncRNA-disease pairs through the condensed gradient boosting model. The results demonstrated that LDA-SCGB greatly outperformed the other four representative LDA inference methods (SDLDA, LDNFSGB, LDAenDL and LDASR) under 5-fold cross validations on lncRNAs, diseases, and lncRNA-disease pairs on three LDA datasets, which were from lncRNADisease v2.0, MNDR, and lncRNADisease v3.0, respectively. LDA-SCGB was further used to find potential lncRNAs for colorectal cancer, heart failure, and lung adenocarcinoma. The results demonstrated that CCDC26, MIAT, and CCDC26 had higher association probability with colorectal cancer, heart failure, and lung adenocarcinoma, respectively.

We foresee that LDA-SCGB was capable of predicting potential lncRNAs for complex diseases and further assisting in cancer diagnosis and therapy.

This review provide a comprehensive overview of the molecular biology and therapeutic advances regarding papillary craniopharyngiomas (PCP), with a particular focus on the pivotal role of the BRAF V600E mutation in its pathogenesis. Histopathologically, PCPs are characterized by stratified squamous epithelium and are frequently associated with the BRAF V600E mutation. This mutation activates the MAPK/ERK signaling pathway, which drives tumor development and progression. The identification of this pathway has led to significant progress in targeted therapies, specifically with the use of BRAF and MEK inhibitors, which have demonstrated remarkable efficacy in clinical trials. These inhibitors can effectively reduce tumor size and improve clinical outcomes for patients. However, despite these advancements, there are challenges such as the potential for resistance to these therapies and the management of long-term side effects. Consequently, a multidisciplinary approach that combines surgical resection, radiation therapy, and targeted therapy is often recommended to enhance treatment efficacy although minimizing adverse effects. In addition to adult cases, this review also addresses rare instances of pediatric PCP. Although these cases are infrequent, their molecular characteristics closely resemble those of adult PCP, suggesting that similar therapeutic approaches might be applicable. Looking ahead, future research should focus on optimizing treatment regimens, understanding the interactions within the tumor's immune microenvironment, and identifying novel therapeutic targets. These efforts are crucial for enhancing precision medicine strategies for PCP patients, ultimately improving their quality of life and long-term prognosis. Overall, continued exploration in this field holds promise for more effective and tailored treatment options.

Acute myeloid leukemia (AML) is the most prevalent type of leukemia in adults, characterized by a complex pathogenesis. The nuclear pore complex is pivotal in the development of various of malignant tumors, including hematological malignancies. While the NUP210 gene is upregulated in several solid tumors, its role in AML remains unreported. RNA-Sequence data and clinical profiles of AML patients were obtained from TCGA databases. Bone marrow samples were obtained from the First Affiliated Hospital of Ningbo University. GEPIA2, UALCAN and TCGA Portal databases were employed for survival prognosis analysis based on NUP210 expression. The GO/KEGG enrichment analysis of NUP210 co-expression and GSEA were performed using R software package. ENCORI and STRING databases were utilized to validate the association between NUP210 and MEIS1, PBX3 or HOXAs. CCK8, RT-qPCR, and Western blot assays were used to detect the viability and related gene expression in AML cell lines.Our findings revealed that NUP210 was significantly upregulated in AML patients compared to healthy controls. Multivariate analyses identified NUP210 as an independent poor prognostic factor in AML. Increased expression of NUP210 inhibited the viability of AML cells. The HOXA9, MEIS1, and PBX3 genes were notably upregulated in the NUP210 high-expression group. The RT-qPCR and Western blot assays demonstrated that NUP210 downregulation in leukemia cells leads to the inhibition of HOXA9 expression. Positive correlations were observed between NUP210 and MEIS1/PBX3, with MEIS1 and PBX3 proteins interacting with the HOXA9 protein. Our results demonstrated that NUP210 was remarkably upregulated in AML and may promote the malignant behavior of AML cells by upregulate HOXA9 gene expression, offering new insights for AML treatment.

Cyclin-dependent kinases regulatory subunit 2 (CKS2) is a key regulator of the cell cycle, but its role in neuroblastoma remains poorly understood. This study investigates the function and mechanisms of CKS2 in neuroblastoma through bioinformatics analyses, as well as in vitro and in vivo experiments. Data from the GEO and TCGA databases indicate that elevated CKS2 expression is associated with poor prognosis in neuroblastoma. Analysis of clinical tumor samples and cell lines further confirmed that CKS2 was significantly overexpressed, particularly in high-risk neuroblastoma patient-derived tissues. Functional studies revealed that CKS2 knockdown reduced cell proliferation and invasion, induced apoptosis, and caused cell cycle arrest in neuroblastoma cells. In vivo, tumors formed from CKS2-silenced cells showed markedly reduced growth. Mechanistically, CKS2 knockdown decreased the phosphorylation of CDK1 (Thr161) and Cyclin B1 (Ser126), suggesting impaired cell division signaling. Treatment with importazole, an importin-β inhibitor, caused CKS2 to accumulate in the cytoplasm rather than in the nucleus, inhibiting proliferation and increasing apoptosis of neuroblastoma cells. Notably, the combination of CKS2 knockdown and importazole treatment produced a stronger anti-tumor effect than either intervention alone. These findings demonstrate that CKS2 promotes neuroblastoma progression by facilitating cell division via the CDK1/Cyclin B1 complex. Targeting CKS2, especially in combination with nuclear import inhibition, offers a promising therapeutic strategy for neuroblastoma.

Prolyl 4-hydroxylase β-subunit (P4HB) is a class of molecular chaperones that inhibits the misfolding of endoplasmic reticulum proteins, and its role in microinvasive adenocarcinoma (MIA) progresses to invasive adenocarcinoma (IAC) is currently unclear. We mined the single-cell dataset GSE189357 to analyze the role of P4HB in LUAD progression. Subsequently, P4HB was overexpressed in H1299 and A549 cell lines, and Galactose lectin-3 binding protein (LGALS3BP) expression was increased and NF-kB pathway was inhibited by PCR and WB. Meanwhile, we also knock down of P4HB in H1299 and A549 cell lines, and the LGALS3BP was decreased and NF-kB pathway was activated. Afterward, the interaction between P4HB and LGALS3BP were verified by Co-IP assays. Meanwhile, the ferroptosis level and the cell proliferation, invasion and metastasis ability were detected under different P4HB expression. Finally, overexpression and knockdown P4HB stable transplants were constructed and verified in vivo. Overexpression of P4HB promoted LUAD cell proliferation (approximately two-fold) and consequently metastasis (approximately two-fold), while inhibiting ferroptosis development, as evidenced by halved ROS production. Clinically, increased P4HB is accompanied by a poor prognosis. Mechanistically, P4HB promotes LGALS3BP expression, suppressing NF-kB pathway activation and thereby driving LUAD progression. P4HB inhibited the activation of the NF-kB pathway by promoting the expression of LGALS3BP, thus promoting the progression of MIA to IAC. This provides a new target for the clinical diagnosis and treatment of LUAD.

Neonicotinoid (NEO) pesticides play a crucial role in agricultural production. However, their potential risks to human health and the environment cannot be overlooked. To gain a comprehensive understanding of the toxicity and mode of action of NEOs, thiamethoxam (THX), which exhibits the highest potential for carcinogenicity and hepatotoxicity, was selected as the subject of this study. We identified 61 intersection genes between THX targets and hepatocellular carcinoma (HCC)-related genes. These genes were then uploaded to the Metascape database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The GO analysis indicated that the significant biological processes mainly involved the response to xenobiotic stimuli, cellular response to chemical stress, cellular response to biotic stimuli, and response to toxic substances. The KEGG enrichment analysis pinpointed several key pathways, primarily including the cell cycle and Glycolysis/Gluconeogenesis. Subsequently, the intersection genes were imported into the Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO) databases to analyze expression differences, leading to the identification of 15 significantly differentially expressed core genes (SDECGs). By applying the Support Vector Machine (SVM) machine-learning model, we screened out five feature genes (CYP2C19, CYP3A4, FBP1, THBS4, CYP7A1) and constructed a nomogram. Molecular docking of THX with these five feature genes showed binding energies of less than -5 kcal/mol. This study offers a theoretical foundation for understanding the underlying mechanisms of THX-induced HCC. The findings provide a scientific basis for the safety assessment of THX in agricultural applications and contribute to the establishment of pesticide safety standards.