Tumor Expansion Research Articles (Page 1)

Anti-tumor activity of CDYL2b in prostate cancer.

DLL4/VEGF bispecific molecularly imprinted nanomissile for robust tumor therapy.

Chimeric antigen receptor (CAR) T cells have long been regarded as living drugs, those activation, diffusion, and expansion influence the clinical efficacy. Dynamic monitoring of CAR-T cells in vivo is crucial for understanding their biodistribution and optimizing therapeutic outcomes. However, due to the challenges in sampling tissue-resident CAR-T cells from patients, limited data have been reported on their spatial and temporal distribution. This study enrolled 43 patients with haematological malignancies receiving CAR-T cell therapy. CAR copy numbers in the peripheral blood (PB) and serous cavity effusion (SCE) were sequentially quantified and analysed. High expansion of CAR-T cells in PB was associated with subsequent expansion in SCE. The median Tmax in SCE occurred later than in PB. Patients with immune effector cell-associated neurotoxicity syndrome (ICANS) exhibited higher CAR copy numbers in cerebrospinal fluid (CSF) compared to those without ICANS. Peripheral infection was associated with increased CAR copy numbers in CSF, which may be caused by cell diffusion or/and expansion. Tumour invasion favored local accumulation and expansion of CAR-T cells in pleural effusion or ascites (PE/A), and patients with tumour invasion had a higher incidence of local cytokine release syndrome (L-CRS). We characterized the spatial and temporal distribution of CAR-T cells and identified associations between CAR copy numbers and local inflammation, tumour invasion, and adverse events. These findings enhance our understanding of CAR-T cells diffusion, trafficking, and expansion, providing novel insights for clinical management and therapeutic optimization.

Insulin‑like growth factor 2 (IGF2) is a multifunctional polypeptide hormone that serves important roles in embryonic development, metabolic regulation and disease pathogenesis. IGF2 expression is tightly regulated by genomic imprinting, which restricts transcription to the paternal allele. IGF2 modulates cellular processes, including proliferation, differentiation and metabolic homeostasis, by activating downstream signaling cascades via binding to IGF1 receptor, insulin receptor isoform A and IGF2 receptor. IGF2 is important for kidney development, promoting both nephron formation, and the functional maintenance of renal tubules and glomeruli. Aberrant IGF2 expression is associated with the pathogenesis of diverse renal diseases, including acute kidney injury, chronic kidney disease, diabetic nephropathy, renal cell carcinoma and Wilms' tumor. Under pathological conditions, IGF2 promotes renal fibrosis and promotes tumor expansion and progression by activating key signaling pathways such as the PI3K/Akt and TGF‑β pathways. Due to these roles, IGF2 has attracted growing clinical interest as a potential therapeutic target. The present review presents a comprehensive analysis of the structure and function of IGF2, its roles in renal pathophysiology, and its therapeutic potential, while outlining future research directions.

Background .Uterine leiomyomas are the most common benign tumors of the female reproductive system, arising from the overgrowth of smooth muscle tissue within the uterus. Typically, they present as solid, spherical masses that are firmer than the surrounding uterine muscle layer. Onset generally occurs between the ages of 30 and 50, with these tumors often located in the uterine body or cervix. Some women may experience gradual tumor enlargement, accompanied by symptoms such as vaginal bleeding, lower abdominal pain, frequent urination, and constipation. In such instances, surgical treatment should be considered the first choice. Case summary In this case, A 59-year-old woman presented with a large, soft, and irregularly shaped uterine leiomyoma, formed by the fusion of hundreds of smaller fibroids, which had metastasized to the sigmoid colon.Immunohistochemical analysis further demonstrated that benign uterine leiomyomas may present with morphological features, consistency, and an invasive growth pattern akin to malignant tumors. Innovations Uterine leiomyomas are benign tumors that rarely metastasize; however, case reports have documented instances of distant metastasis. Conclusion The purpose of this study is to report a case of a uterine leiomyoma with intestinal metastasis, analyze its rare characteristics and invasive growth pattern, and enhance the understanding of this tumor.

BACKGROUND Tenosynovial giant cell tumor (TGCT) can be characterized as localized when it occurs in the fingers and wrist, or diffuse, when it occurs in large weight-bearing joints, such as hips, knees, and ankles. However, the occurrence of TGCT in the coracoclavicular ligament is rare and has not been reported in the literature. In this case, inexperienced doctors are prone to misdiagnosis or underdiagnosis, which in turn leads to patients not being able to get the correct treatment in time. CASE REPORT This is a report of a 16-year-old female patient with symptoms of right shoulder pain and movement limitation for 1 month, aggravated for 1 week. She had received medication and physical therapy at an outside hospital, but with no improvement in her symptoms. She was admitted to our hospital and underwent tumor resection after complete imaging examination, and tissue specimens were taken for pathological examination. Pathologic results suggested TGCT. After surgery, the shoulder function gradually returned to normal. There was no sign of tumor recurrence in the right shoulder at 6 months, 1 year, and 2 years postoperatively. CONCLUSIONS This rare case shows that TGCT should be considered when a nodular lesion with equisignal in the T1-weighted image and mixed signals in the T2-weighted image is visualized on magnetic resonance imaging, and when computed tomography suggests a circumferential calcified lesion at the margin. Early diagnosis, treatment, and long-term follow-up after surgery can effectively reduce tumor expansion and recurrence risk.

Worldwide, breast carcinoma represents the single most widespread disease among women as well as the second most prevalent malignancy overall. This condition is heterogeneous, comprising multiple distinguished subgroups characterized by unique gene transcription variations and varying mortality rates. Multiple diverse studies suggest that estrogen receptor gene polymorphisms might impact BC susceptibility and formation, which may alter receptor function, tumor expansion, and sensitivity to hormonal therapies. These genes regulate estrogen signaling pathways, affecting breast cancer (BC) formation. The linkage of various polymorphisms of ESR2 gene on BC development is not comprehended. Hence, our objective was to scrutinize the correlation among the ESR2 (rs3020449) polymorphism and BC risk in Bangladeshi women. A case-control genetic association study was undertaken on 209 clinically diagnosed BC female patients against 201 healthy women of Bangladeshi ethnicity using the amplification refractory mutation system polymerase chain reaction (ARMS-PCR). We evaluated p-value, odds ratio (OR) and 95% confidence interval (95% CI) for comprehending the level of risk association of rs3020449. This SNP showed reduced risk in AG vs. AA (heterozygous/additive) model where, OR = 0.58, 95% CI = 0.38 to 0.90, p = 0.015. Moreover, rs3020449 indicated a lower tumor aggressiveness in tumor grade (II vs. I) with the statistics of OR = 0.3138, 95% CI = 0.10 to 0.96, p = 0.043 and in tumor staging, both stage-II (OR = 0.37, 95% CI = 0.15 to 0.90, p = 0.028) and stage-IV (OR = 0.16, 95% CI = 0.05 to 0.53, p = 0.002) against Stage-I. The findings of the research suggested that ESR2 (rs3020449) polymorphism may decrease the risk of BC formation and progression in Bangladeshi women.

ObjectiveTo investigate the mechanism of hsa_circ_0075451 in promoting NSCLC proliferation, metastasis, and glycolysis through interaction with RBM4.MethodsCancerous tissues and paracancerous tissues were collected from 53 cases of NSCLC. RT-qPCR or Western blot was performed to detect hsa_circ_0075451 and RBM4. Relevant sequences or plasmids were transfected into NSCLC cell line A549, and the malignant phenotype of NSCLC cells was detected by CCK-8, EdU, AnnexinV-PI double staining assay, and Transwell. Glycolysis was assessed by glucose consumption, lactic acid production, and glycolysis-related proteins. In vivo tumorigenesis assays were performed to investigate hsa_circ_0075451 functions in NSCLC. Mechanistic studies were analyzed to verify the interaction of hsa_circ_0075451 and RBM4.ResultsHsa_circ_0075451 levels were elevated in NSCLC, and reducing its expression diminished cell proliferation, metastasis, glycolysis, and tumor expansion. Hsa_circ_0075451 interacted with RBM4. RBM4 down-regulation restricted NSCLC cell proliferation, metastasis, and glycolysis. RBM4 up-regulation opposed the effects of hsa_circ_0075451 knockdown.ConclusionHsa_circ_0075451 promotes NSCLC proliferation, metastasis and glycolysis by interacting with RBM4.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12672-025-03330-4.

Stem cells can generate differentiated progeny directly or indirectly through transit-amplifying progenitors (TAPs), which are vulnerable to tumorigenic transformation. Despite clinical relevance, how stem cells regulate TAP production is unclear. Drosophila brains contain Asense+ stem cells (Type1 neuroblasts; T1NBs) that generate low neurogenic potential TAPs and Asense- stem cells (Type2 neuroblasts; T2NBs) that produce high-potential TAPs [Intermediate Neural Progenitors (INPs)]. Unexpectedly, cell-type-specific enhancers of genes essential for INP formation are poised in T1NBs despite never generating INP progeny. Thus, both NB types are competent to generate INPs. Inducing T1NBs to generate INPs is more efficient upon asense knockdown. The progeny of T2NBs expressing elevated Asense adopt a low-potential TAP identity instead of INPs. Elevated Asense expression limits tumor NB expansion driven by stalled INPs halting tumor expansion. We propose that a double-assurance mechanism characterized by dynamic superimposition of lineage-specific activators upon basal-state determinants defines NB capability to generate high-potential TAPs.

Intramedullary spinal cord tumors are rare and often difficult to resect due to infiltration of the cord parenchyma. Surgeons may elect to perform an expansile duraplasty after resection, although the impact of duraplasty on postoperative outcomes has not been well-characterized. Therefore, we examine the characteristics and outcomes of patients receiving duraplasty after resection of intramedullary astrocytomas. Adult patients undergoing surgical resection of a primary spinal cord astrocytoma between 2003 and 2023 at a single tertiary care hospital were retrospectively identified. Cohort characteristics were collected from patient charts. Data were analyzed using the Wilcoxon rank-sum and Fisher exact tests. Multivariable analyses investigated the impact of duraplasty on postoperative outcomes. Subgroup analyses were performed on patients who underwent subtotal resection and on a propensity score matched cohort based on age and body mass index. Fifty-nine patients were identified, with 14 (24%) receiving expansile duraplasty. Patients with duraplasty were more likely to experience longer hospitalizations (median 9 vs 5 days; P < .01), undergo subtotal resection (100% vs 60%; P < .01), and be discharged to acute care inpatient rehabilitation (79% vs 40%; P = .02). They had higher rates of chemotherapy (71% vs 31%; P = .01), cerebrospinal fluid leaks (21% vs 2%; P = .04), worse functional outcomes at last follow-up (71% vs 42% modified McCormick scale > 2; P = .05), and mortality at last follow-up (79% vs 27%; P < .01) than those without duraplasty. Currently, duraplasty remains an option based on surgeon judgment, typically in situations when intraoperative swelling occurs, dural closure is not possible, or postoperative cord or tumor expansion is anticipated. With current patient selection practices, providers and patients should be aware of the differences often seen in the postoperative course and appropriately weigh the risks of added surgical complexity against the potential for meaningful improvements in patient quality of life and survival.

In this article, we proposed a simplified mathematical model of primary tumor growth that involves four cell populations: Two types of cancer cells with different levels of immunogenicity, and the immune response in its two components, innate and adaptive. By varying the proliferation rate of non-immunogenic cancer cells and the innate immune stimulation parameter, and applying biparametric numerical continuation techniques, we identified distinct stability regions that revealed scenarios of tumor escape and latency. A closed curve of supercritical Hopf bifurcation points was also detected, delineating the parameter region in which limit cycles emerged. By examining the population maxima of each cell type at steady state, we identified parameter values at which both immunogenic and non-immunogenic tumor cell populations remain in stable equilibrium at modest levels, sustained by an immune response that does not escalate to intensities associated with immunological damage.

Breast cancer is hallmarked by phenotypic transitions enabling abnormal cell proliferation and invasion. The stress-protective transcription factor heat shock factor 2 (HSF2) is associated with cancer, but its function in breast carcinogenesis remains poorly understood. Analysis of human breast tumor samples and mouse in vivo xenografts uncovered that HSF2 expression and activity undergo dynamic changes as a function of tumor progression. HSF2 expression, nuclear localization, and coexpression with the proliferation marker Ki67 are increased in ductal carcinoma in situ (DCIS), suggesting that HSF2 designates hyperplastic cells underlying tumor expansion. In mouse xenografts, HSF2 localization switches from nuclear to cytoplasmic upon DCIS-to-invasive transition. Using cell-based models, we identify canonical transforming growth factor–β (TGF-β) signaling as the molecular mechanism regulating HSF2. TGF-β–mediated down-regulation of HSF2 allowed acquisition of an invasive cell phenotype, which was counteracted by ectopic HSF2. Together, we propose that HSF2 acts as a stage-specific switch between proliferation and invasion in breast cancer.

Tumour growth involves dynamic interactions among tumour cells, extracellular materials, and host tissue. The tumour exerts mechanical stresses on the host tissue and simultaneously experiences compression across the tumour-host interface. This article presents a mathematical model that mimics an in vivo set-up, where an avascular tumour is surrounded by healthy/normal tissue, utilizing conservation principles for the constituents in each region. Tumour and host tissues are separately treated as biphasic mixtures comprising cells and extracellular materials. This study incorporates the diffusion-dominated transport and metabolism of cell-nourishing agents (CNA), such as oxygen, nutrients, and growth factors. The mechanical impact of normal host tissue on tumour growth dynamics while maintaining stress continuity at the tumour-host interface is analysed through numerical simulations. The key findings are that when CNA levels decline below a specific threshold, the tumour cell volume fraction decreases from the periphery to the centre, resulting in necrotic cell death alongside apoptosis. This study indicates that host tissue reduces CNA tension, accelerating tumour necrosis. The increased viscosity of normal host cells indicates stronger intercellular bonds, causing the cells to adhere more tightly and stiffen the host. With increasing viscosity-induced resistance, the host tissue more effectively impedes tumour expansion, thereby slowing tumour growth due to rising compressive stress. Analytical results for a solvable scenario are also provided to explore the comparative behaviour with numerical simulations of the complete model. Furthermore, analytical results indicate that an increased viscosity of normal host tissue may delay the initiation of necrotic cell death.

Sponsored by BC Cancer FoundationIntroduction: Glioblastoma (GBM) cells infiltrate deep brain structures by exploiting perivascular pathways, utilizing stem-like properties and malignant traits to access nutrient-rich environments that support tumor expansion. Our findings suggest that N-methyl-D-aspartate receptors (NMDARs) in brain endothelial cells play a key role in transducing signals initiated by parenchymal cells, facilitating recurrent GBM progression. Hypothesis: D-serine enhances GBM migration and stemness by interacting with host endothelial cells, thereby promoting recurrent tumor aggressiveness. Methods: Patient-derived recurrent GBM cells and human cerebral microvascular endothelial cells (hCMECs/D3) were co-cultured in a transwell system to assess the role of endogenous D-serine in GBM migration and stemness. Pharmacological inhibitors, CRISPR/Cas9-mediated gene silencing, and enzymatic modulation of D-serine metabolism were employed to determine the contribution of GBM-derived D-serine and endothelial NMDARs to these processes. Further, in vivo xenograft experiments employed gene silencing or pharmacological inhibitors of Serine Racemase (SRR) to test the effects of recurrent tumorigenesis. Results: Endothelial cells significantly potentiated GBM migration and stemness in co-culture. D-serine release from GBM cells was confirmed using D-amino acid oxidase, SRR inhibition with phenazine methosulfate (PMS), and CRISPR-mediated SRR silencing, significantly reducing migration and stemness markers. Pharmacological NMDAR antagonism and endothelial GluN1 silencing further mitigated these effects. In vivo, SRR silencing, or inhibition, reduced tumor burden at 4 weeks post-injection and extended survival in GBM-bearing mice. Conclusion: Our findings demonstrate that brain endothelial cells enhance GBM malignancy through D-serine- mediated activation of endothelial NMDARs. This pathway supports GBM migration and stemness, presenting a novel therapeutic target for recurrent GBM treatment.

As one of the most prevalent malignancies worldwide, colorectal cancer (CRC) exhibits a strong metabolic dependency on glycolysis, which fuels tumor expansion and shapes an immunosuppressive microenvironment. Despite its clinical significance, the regulatory landscape and cellular diversity of glycolytic metabolism in CRC require systematic exploration. Multi-omics datasets (bulk/scRNA-seq and spatial transcriptomics) were analyzed to quantify glycolytic signatures. Core regulatory genes were selected via integrated pathway mapping and a machine learning framework incorporating five-feature selection algorithms. Cellular subpopulations were delineated by metabolic profiles, with niche interactions modeled through ligand-receptor network analysis. Findings were validated across multicenter cohorts. Our analyses identified a tumor subpopulation characterized by a High Glycolytic State (HGS), displaying elevated glycolytic signature alongside stem-like properties. Spatial profiling demonstrated relative enrichment of HGS cells in central tumor regions, potentially reflecting adaptation to nutrient-limited conditions. Among the molecular features associated with HGS maintenance, five candidate regulators (PFKP, ERO1A, FKBP4, HDLBP, HSPA5) showed correlation with unfavorable clinical outcomes. Our study characterizes the metabolic heterogeneity of CRC and suggests a potential role for HGS cells in shaping the tumor microenvironment. The molecular features identified here may offer insights into metabolic dependencies that could be explored for future therapeutic targeting.

Obesity is an established risk factor for breast cancer (BC), yet the specific mechanisms driving this association remain unclear. Dysregulated lipid metabolism has emerged as a key factor in cancer cell biology, and, while obesity is often accompanied by hyperlipidemia, the isolated impact of elevated lipid levels on BC growth has not been experimentally tested. Using the E0771 and Py230 orthotopic models of obesity-accelerated BC growth in immune-competent mice, we investigated the role of systemic lipids on tumor growth. Combining dietary and genetic mouse models, we show that elevated circulating lipids are sufficient to accelerate BC tumor growth even in the absence of obesity or alterations in blood glucose and/or insulin levels. Pharmacological lowering of systemic lipid levels attenuates BC growth in obese mice, suggesting a direct role for lipids in fueling tumor expansion. Notably, we also show that weight loss alone, without a corresponding reduction in lipid levels such as that induced by a ketogenic diet, fails to protect against BC, highlighting the necessity of targeting lipid metabolism in obesity-associated BC. Our findings establish hyperlipidemia as a critical driver of BC progression and suggest that lipid-lowering interventions may be a promising strategy to mitigate BC risk in individuals with obesity.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40170-025-00407-0.

Chronic antigen exposure in the tumor microenvironment drives CD T cell exhaustion, marked by increased inhibitory receptors and diminished effector functions. Immune checkpoint blockade seeks to prevent or reverse exhaustion, but its success relies on the pre-existing state of tumor-infiltrating T cells. To investigate this, we developed a mathematical model examining: (1) how T cell exhaustion disrupts tumor-immune equilibrium, (2) anti-PD-L1 efficacy across exhaustion states, and (3) efficacy of next-generation therapies (e.g., IFN -anti-PD-L1, PD1-IL2v). Stability analysis and simulations reveal that tumor PD-L1 expression critically influences immune dynamics, particularly the bistability of tumor-free and tumorous states. High PD-1 expression and exhaustion rates correlate with growth of tumor and impaired expansion of less-exhausted CD T cells. While anti-PD-L1 efficacy depends on baseline exhaustion, severe exhaustion enables immune escape. Next-generation therapies enhancing cytotoxicity and sustaining less-exhausted T cell populations show improved tumor control, suggesting combination strategies may overcome resistance.

ObjectiveAn optimal surveillance plan of micro-nonfunctioning pituitary adenomas (micro-NFPAs) is not well established despite high prevalence and increasing incidence of these tumors. This study aims to characterize the natural history of conservatively treated micro-NFPAs and provide evidence for a management algorithm.MethodsRetrospective, single center cohort study that analyzed clinical, hormonal and imaging data of conservatively managed micro-NFPAs (years 2018-2023).Results371 patients with micro-NFPAs were included in the study (mean age at diagnosis 41.26 ± 13.71 years, 91.6% females) with a mean tumor size at detection of 5.51 ± 1.95 mm. Over a median follow-up period of 4.8 years (IQR 2-8.64): 23.7% of all micro-NFPAs were stable, 41% regressed and 35.3% had any progression in size (34.5% of patients had a significant tumor growth, when considering 1 mm enlargement as significant, with a growth incidence of 17.18 per 100 person-years, 95% CI: 14.2- 20,15). The median growth was 1 mm (IQR: 0.5-2) over the entire follow up period and only 2.42% microadenomas evolved into macroadenomas, without clinical consequences. Sex, BMI, age were not predictors of tumor growth, however tumors smaller than 6 mm had a 47.4% higher incidence rate of significant tumor growth (≥ 1mm) events per 100 person-years, compared to larger microadenomas. Alternating CT with MRI during follow-up is an important predictor for tumor variability. Median time until growth was 11.32 months (95%CI: 9.66- 12.97). At diagnosis, 1.1% had secondary hypogonadism, 1.1% hypothyroidism and 0.5% secondary hypoadrenalism. During follow-up, only 5 patients (1.3%) developed hypopituitarism after a median of 2 years (0.9-5.1), irrespective of tumor enlargement or other demographic and clinical factors.ConclusionMicro-NFPAs have an overall benign clinical course, with a high measuring variability in tumors smaller than 6 mm and hypopituitarism is a very rare occurrence. Performing the first follow-up MRI at one year and if stable, delaying re-evaluation to 5 years, without pituitary function reassessment in absence of clinical manifestations, is a safe and cost-effective approach.

Interactions in hepatic tumor microenvironment: Potential targets and modulations for effective therapy.

Stromal reprogramming in solid tumors by nanoparticles: A review.