Tumor Invasion Research Articles

Advances in the regulation of the role of Myeloid-derived suppressor cells in the Tumor microenvironment by Tumor-derived exosomes

In the progression of malignancies, myeloid-derived suppressor cells (MDSCs) play a crucial role in modulating tumor immunology within the tumor microenvironment (TME), which is often characterized by the extensive infiltration of immune cells. These cells are abnormally activated and demonstrate strong immunosuppressive properties under pathological conditions such as cancer. Recent research highlights the importance of tumor-derived exosomes (TEXs) as key mediators of this immunosuppressive activity. TEXs, small extracellular vesicles released by tumor cells, carry a diverse array of bioactive molecules such as proteins, lipids, and RNA, which modulate the behavior of recipient cells within the TME. The assembly and release of TEXs are tightly regulated by the TME, and accumulating evidence suggests that TEXs facilitate MDSC activation, expansion, and enhancement of their immunosuppressive functions. This study aims to investigate the role of TEXs in mediating intercellular communication between tumor cells and MDSCs. By understanding these mechanisms, it is possible to develop strategies to regulate MDSC behavior, including promoting their differentiation into mature myeloid cells, reducing their expansion and accumulation, and impairing their suppressive activity. Ultimately, these insights will provide a foundation for targeting MDSCs as a therapeutic approach to inhibit tumor growth, invasion, and metastasis, offering promising directions for future clinical applications.

MicroVasculoid‐Chip: A 3D Self‐Assembled Human Microcirculation‐on‐a‐Chip Model Reveals Enhanced Lymphangiogenic Lung Cancer‐Induced Vessel Remodeling and Invasion

AbstractThe microvasculature within the tumor microenvironment is crucial for the invasion and dissemination of cancer cells throughout the body. Given its importance and dynamic behavior, several microfluidic models have been developed to study microvascular infiltration and its interaction with cancer cells. However, most of these models primarily focus on blood vessels and use microfluidic channels coated with endothelial cells, which fail to replicate near‐physiological conditions. To address this limitation, the MicroVasculoid‐chip is introduced, a novel human microcirculation‐on‐a‐chip model that features self‐organized 3D blood and lymphatic microvasculature alongside tumor spheroids. This innovative platform enables the exploration of interactions between multi‐cellular tumors and both microvascular networks. Using lung cancer as a case study, how tumor‐released mediators influence vessel morphology is investigated in relation to tumor invasion capacity, identifying molecular factors potentially associated with microvascular remodeling. Overall, the MicroVasculoid‐chip provides a robust tool for investigating and modeling critical events of cancer neo‐vascularization, for deciphering fundamental mechanisms of cancer cell invasion into the microvasculature, and for future drug screening applications.

Spatial Distribution of Tumor Cells in Clear Cell Renal Cell Carcinoma Is Associated with Metastasis and a Matrisome Gene Expression Signature

Background/Objectives: Predicting the behavior of clear cell renal cell carcinoma (ccRCC) is challenging using standard-of-care histopathologic examination. Indeed, pathologic RCC tumor grading, based on nuclear morphology, performs poorly in predicting outcomes of patients with International Society of Urological Pathology/World Health Organization grade 2 and 3 tumors, which account for most ccRCCs. Methods: We applied spatial point process modeling of H&E-stained images of patients with grade 2 and grade 3 ccRCCs (n = 72) to find optimum separation into two groups. Results: One group was associated with greater spatial randomness and clinical metastasis (p < 0.01). Notably, spatial analysis outperformed standard pathologic grading in predicting clinical metastasis. Moreover, cell-to-cell interaction distances in the metastasis-associated group were significantly greater than those in the other patient group and were also greater than expected by the random distribution of cells. Differential gene expression between the two spatially defined groups of patients revealed a matrisome signature, consistent with the extracellular matrix’s crucial role in tumor invasion. The top differentially expressed genes (with a fold change > 3) stratified a larger, multi-institutional cohort of 352 ccRCC patients from The Cancer Genome Atlas into groups with significant differences in survival and TNM disease stage. Conclusions: Our results suggest that the spatial distribution of ccRCC tumor cells can be extracted from H&E-stained images and that it is associated with metastasis and with extracellular matrix genes that are presumably driving these tumors’ aggressive behavior.

Virulence factor discovery identifies associations between the Fic gene family and Fap2+ fusobacteria in colorectal cancer microbiomes.

Fusobacterium is a bacterium associated with colorectal cancer (CRC) tumorigenesis, progression, and metastasis. Fap2 is a fusobacteria-specific outer membrane galactose-binding lectin that mediates Fusobacterium adherence to and invasion of CRC tumors. Advances in omics analyses provide an opportunity to profile and identify microbial genomic features that correlate with the cancer-associated bacterial virulence factor Fap2. Here, we analyze genomes of Fusobacterium colon tumor isolates and find that a family of post-translational modification enzymes containing Fic domains is associated with Fap2 positivity in these strains. We demonstrate that Fic family genes expand with the presence of Fap2 in the fusobacterial pangenome. Through comparative genomic analysis, we find that Fap2+ Fusobacteriota are highly enriched with Fic gene families compared to other cancer-associated and human gut microbiome bacterial taxa. Using a global data set of CRC shotgun metagenomes, we show that fusobacterial Fic and Fap2 genes frequently co-occur in the fecal microbiomes of individuals with late-stage CRC. We further characterize specific Fic gene families harbored by Fap2+ Fusobacterium animalis genomes and detect recombination events and elements of horizontal gene transfer via synteny analysis of Fic gene loci. Exposure of a F. animalis strain to a colon adenocarcinoma cell line increases gene expression of fusobacterial Fic and virulence-associated adhesins. Finally, we demonstrate that Fic proteins are synthesized by F. animalis as Fic peptides are detectable in F. animalis monoculture supernatants. Taken together, our study uncovers Fic genes as potential virulence factors in Fap2+ fusobacterial genomes.IMPORTANCEAccumulating data support that bacterial members of the intra-tumoral microbiota critically influence colorectal cancer progression. Yet, relatively little is known about non-adhesin fusobacterial virulence factors that may influence carcinogenesis. Our genomic analysis and expression assays in fusobacteria identify Fic domain-containing genes, well-studied virulence factors in pathogenic bacteria, as potential fusobacterial virulence features. The Fic family proteins that we find are encoded by fusobacteria and expressed by Fusobacterium animalis merit future investigation to assess their roles in colorectal cancer development and progression.

Targeting glycolysis: exploring a new frontier in glioblastoma therapy

Glioblastoma(GBM) is a highly malignant primary central nervous system tumor that poses a significant threat to patient survival due to its treatment resistance and rapid recurrence.Current treatment options, including maximal safe surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, have limited efficacy.In recent years, the role of glycolytic metabolic reprogramming in GBM has garnered increasing attention. This review delves into the pivotal role of glycolytic metabolic reprogramming in GBM, with a particular focus on the multifaceted roles of lactate, a key metabolic product, within the tumor microenvironment (TME). Lactate has been implicated in promoting tumor cell proliferation, invasion, and immune evasion. Additionally, this review systematically analyzes potential therapeutic strategies targeting key molecules within the glycolytic pathway, such as Glucose Transporters (GLUTs), Monocarboxylate Transporters(MCTs), Hexokinase 2 (HK2), 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), Pyruvate Kinase Isozyme Type M2 (PKM2), and the Lactate Dehydrogenase A (LDHA). These studies provide a novel perspective for GBM treatment. Despite progress made in existing research, challenges remain, including drug penetration across the blood-brain barrier, side effects, and resistance. Future research will aim to address these challenges by improving drug delivery, minimizing side effects, and exploring combination therapies with radiotherapy, chemotherapy, and immunotherapy to develop more precise and effective personalized treatment strategies for GBM.

Effects of macrophages in OSCC progression

Macrophages are crucial immune cells within the tumor microenvironment (TME), involved in regulating tumor proliferation, invasion, metastasis, ECM remodeling, angiogenesis, and immunosuppression. Although more and more experimental evidence and clinical data indicate that macrophages are involved in the onset and progression of oral squamous cell carcinoma (OSCC), the exact pathogenesis of OSCC associated with macrophages has not been fully elucidated. Enhanced knowledge of the molecular mechanisms involving macrophages in OSCC will aid in the creation of treatments targeted specifically at macrophages. This review outlines the pro-tumoral and anti-tumoral effects of macrophages in OSCC, emphasizing the interaction between OSCC cells and macrophages. It can provide theoretical basis for the establishment of complex regulatory network centered on macrophages and explore novel therapeutic strategies for OSCC.

Phosphatidylinositol promoted the proliferation and invasion of pituitary adenoma cells by regulating POU1F1 expression

Invasiveness of pituitary adenoma is the main cause of its poor prognosis, mechanism of which remains largely unknown. In this study, the differential proteins between invasive and non-invasive pituitary tumors (IPA and NIPA) were identified by TMT labeled quantitative proteomics. The differential metabolites in venous bloods from patients with IPA and NIPA were analyzed by untargeted metabolomics. Proteomic data showed that the top five up-regulated proteins were AD021, C2orf15, PLCXD3, HIST3H2BB and POU1F1, and the top five down-regulated proteins were AIPL1, CALB2, GLUD2, SLC4A10 and GTF2I. Metabolomic data showed that phosphatidylinositol (PI) was most remarkably up-regulated and melibiose was most obviously down-regulated. Further investigation demonstrated that PI stimulation increased the expression of PITPNM1, POU1F1, C2orf15 and LDHA as well as the phosphorylation of AKT and ERK, and promoted the proliferation, migration and invasion of GH3 cells, which were blocked by PITPNM1knockdown. Inhibiting AKT phosphorylation reduced the expression of POU1F1, C2orf15 and LDHA in PI-stimulated cells while activating AKT increased their expression in PITPNM1-silencing cells, which was similar to the function of ERK. POU1F1 silence suppressed the expression of LDHA and C2orf15. Luciferase report assay and ChIP assay demonstrated that POU1F1 positively regulated the transcription of LDHA and C2orf15. In addition, PI propelled the metastasis of GH3 cells in vivo, and elevated the expression of PITPNM1, POU1F1, C2orf15 and LDHA. These results suggested that elevated serum PI might contribute to the proliferation and invasion of pituitary adenoma by regulating the expression of PITPNM1/AKT/ERK/POU1F1 axis.

Obesity alters the fitness of peritumoral adipose tissue, exacerbating tumor invasiveness in renal cancer through the induction of ADAM12 and CYP1B1.

Obesity exacerbates the risk and aggressiveness of many types of cancer. Adipose tissue (AT) represents a prevalent component of the tumor microenvironment (TME) and contributes to cancer development and progression. Reciprocal communication between cancer and adipose cells leads to the generation of cancer-associated adipocytes (CAAs), which in turn foster tumor invasiveness by producing paracrine metabolites, adipocytokines, and growth factors. Interfering with the crosstalk between CAAs and cancer cells is of key relevance in the prevention of tumor progression. The present study aimed to analyze the contribution of peritumoral AT in renal cell carcinoma (RCC) progression in lean versus overweight or obese patients. By isolating human adipose-derived stromal/stem cells from the three groups of patients and performing conditioned medium studies with RCC cells along with in vivo xenograft experiments, we found that peritumoral adipocytes from the three groups show a distinct expression profile of genes. In particular, ADAM metallopeptidase domain 12 (ADAM12) and cytochrome P450 family 1 subfamily B member 1 (CYP1B1) were found to be upregulated in obesity and their silencing reduced RCC cell invasiveness. In conclusion, high ADAM12 and CYP1B1 expressions in the peritumoral adipocytes boost tumor invasiveness and may serve as an indicator of poor prognosis in RCC.

3D Bioprinted Head and Neck Squamous Cell Carcinoma (HNSCC) Model Using Tunicate Derived Nanocellulose (NC) Bioink.

Head and neck squamous cell carcinoma (HNSCC) are invasive solid tumors accounting for high mortality. To improve the clinical outcome, a better understanding of the tumor and its microenvironment (TME) is crucial. Three -dimensional (3D) bioprinting is emerging as a powerful tool for recreating the TME in vitro. To establish long-term HNSCC bioprinted constructs for personalized drug-testing, this proof-of-principle study aims to compare two different innovative tunicate-derived nanocellulose (NC) hydrogels against the widely used semi-synthetic gelatin methacryloyl (GelMA). Cell lines of different tumor origin sites are printed in TEMPO and Carboxy-NC, and GelMA in alginate (GelMAA). Both NC hydrogels show higher bioprintability than GelMAA. Carboxy-NC supported long-term HNSCC survival, proliferation, and maintenance of epithelial phenotype in 3D bioprinted constructs similar to GelMAA. The hydrogel microstructure revealed differences in pore size. Importantly, the established HNSCC bioprinted model allowed the testing of radiochemotherapy (RCT) both in cell lines and patient-derived cultures. Compared to a spheroid model, the cytotoxic effects are less, better reflecting the response in patients. The proof-of-principle findings indicate that Carboxy-NC is a viable alternative to gelatin-based bioink with improved bioprintability allowing personalized drug-testing. By adding other cell-types of the TME, this model can be advanced to a heterotypic one.

The Pharmacological Research of Traditional Chinese Medicine and Herbal Remedies in the Treatment of Melanoma

Background: Melanoma is a highly invasive and metastatic malignant tumor, with pathogenesis involving multiple signaling pathways and transcription factors. Current treatments face significant challenges, including drug resistance, toxic side effects, and recurrence. Purpose: This review aims to evaluate the therapeutic potential of natural products in the treatment of melanoma and to identify the associated challenges and future research opportunities. Methods: A comprehensive literature search was conducted using PubMed and Web of Science to identify studies reporting on natural products with antimelanoma activity. Results: Natural products demonstrate diverse pharmacological activities, including antiproliferative, proapoptotic, and antimetastatic effects, highlighting their potential in melanoma treatment. However, challenges such as limited efficacy, safety concerns, and the lack of standardized formulations remain significant barriers. Conclusion: This review provides insights into the therapeutic applications of natural products for melanoma, discusses existing limitations, and proposes future directions, contributing to the development of effective and safe antimelanoma treatments.

Cervical Tuberculosis Mimicking Cervical Cancer in a Postmenopausal Woman: A Case Report

Cervical tuberculosis is a rare form of genital tuberculosis. A case of a 73-year-old woman who presented with cervical wall thickening on magnetic resonance imaging, suggesting an invasive malignant neoplasm, is documented. Cervical cone excision was performed for histopathological study. Microscopy showed epithelioid granulomas, without appreciable caseous necrosis, in the wall of the uterine cervix, associated with erosion of the overlying cervical mucosa. Histochemical stains for microorganisms (Ziehl–Neelsen, Grocott, and Warthin–Starry) were negative. Immunohistochemistry for Treponema pallidum revealed scarce, spiral-shaped bacilli, which raised the diagnostic possibility of secondary syphilis. The serological study for syphilis was negative, however. Polymerase chain reaction (PCR) tests for Mycobacterium tuberculosis and Treponema pallidum were performed in the formaldehyde-fixed, paraffin embedded tissue and resulted positive for Mycobacterium tuberculosis and negative for Treponema pallidum, confirming the diagnosis of cervical tuberculosis. Our objective was to report a rare case of cervical tuberculosis, discussing the advantages and limitations of complementary techniques used in the pathological diagnosis of infectious agents and highlighting diagnostic pitfalls. In conclusion, correct microbiological diagnosis requires the implementation of integrated workflows employing complementary techniques in a multidisciplinary setting to improve the accuracy of histopathological examination in infectious diseases.

Interplay and clinicopathological correlates of tumor size, multifocality and aggressive variants in patients with operated differentiated thyroid carcinoma: A retrospective cohort study

Objectives: To investigate the interplay and clinicopathological correlates of tumor size, cancer foci (multifocality/bilaterality), and aggressive variants in patients with operated differentiated thyroid cancer (DTC). Methods: A total of 596 patients with operated DTC (median age: 47.0 (range: 18.0-87.0 years, 77.5% were females) were included in this retrospective cohort study. Data on patient demographics, cancer foci, concomitant Hashimoto's thyroiditis, surgery type, DTC subtype (papillary thyroid cancer [PTC], follicular thyroid cancer [FTC]) and variants, tumor size, lymph node metastasis, tumor invasion were recorded. Results: PTC aggressive variant (21.9%, P=0.045), extrathyroidal invasion (24.6%, P=0.012), tall cell PTC variant (60.3%, P=0.043), and widely invasive FTC variants (60.0% P=0.002) rates were significantly higher in the bilateral multifocal tumors than in the unifocal and unilateral multifocal tumors. The rates of Hashimoto's thyroiditis (59.8%, P<0.001) and PTC subtype (99.6%, P<0.001) were significantly higher, while the rates of lymph node metastasis (5.8%, P<0.001), capsule invasion (11.6%, P<0.001), vascular invasion (0.4%, P<0.001) and extrathyroidal invasion (4.5%, P<0.001) were significantly lower in <10 mm than in >10 mm tumors. Presence vs. absence of PTC aggressive variant was associated with significantly higher greatest tumor size (12 mm, P=0.013) and higher rates of multifocal tumor (50.5%, P=0.013) and extrathyroidal invasion (33.0%, P<0.001). Conclusions: Our findings revealed the presence of bilaterality/multifocality and aggressive variants in a considerable proportion of patients with operated DTC, and a multifaceted interplay between bilaterality/multifocality, tumor size, and PTC aggressive variants, in addition to their individual effects on increased risk of tumor invasion, particularly the extrathyroidal invasion.

Interrogation of the Tumor Microenvironment by Nanoparticles.

The tumor microenvironment (TME) plays a pivotal role in cancer progression by fostering intricate multicellular crosstalk among cancer cells, stromal cells, and immune cells. This review explores the emerging paradigm of utilizing nanoparticles to disrupt this crosstalk within the TME as a therapeutic strategy. Nanoparticles are engineered with precise physicochemical properties to target specific cell types and deliver therapeutic payloads, thereby inhibiting critical signaling pathways involved in tumor growth, invasion, and metastasis. The mechanisms involved include modulation of the immune response, interference with growth factor signaling, and induction of programmed cell death in cancer cells. Challenges such as biocompatibility, efficient delivery, and potential development of resistance are discussed alongside promising advancements in nanoparticle design. Moving forward, integration of nanoparticle-based therapies with existing treatment modalities holds great potential for enhancing therapeutic efficacy and personalized medicine in cancer therapy.

Comparison of 11C-Acetate and 18F-FDG PET/CT for Immune Infiltration and Prognosis in Hepatocellular Carcinoma.

Immunotherapy has revolutionized cancer treatment, making it a challenge to noninvasively monitor immune infiltration. Metabolic reprogramming in cancers, including hepatocellular carcinoma (HCC), is closely linked to immune status. In this study, we aimed to evaluate the ability of carbon-11 acetate (11C-acetate) and fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT findings in predicting overall survival (OS) and immune infiltration in HCC patients. Totally 32 patients who underwent preoperative 18F-FDG and 11C-acetate PET/CT, followed by liver resection for HCC, were prospectively enrolled at authors' institute between January 2019 and October 2021. Tracer uptake was qualified. Densities of CD3+, CD8+, and granzyme B+ CD8+ immune cells were assessed and the Immunoscore was defined by combining the densities of CD3+ and CD8+ in tumor interior (TI) and invasion margin (IM). Patients with avid HCCs in 11C-acetate PET/CT demonstrated a longer OS. Those with only 11C-acetate-avid HCCs exhibited a longer OS compared to those with only 18F-FDG uptake. In contrast to 18F-FDG uptake, 11C-acetate uptake was positively associated with CD3+, CD8+, and granzyme B+ CD8+ cell infiltration. Patients with a higher Immunoscore exhibited a longer OS and an increased uptake of 11C-acetate rather than 18F-FDG. The sensitivity of 11C-acetate PET/CT in the detection of patients with immune infiltration was superior to that of 18F-FDG PET/CT (88% [21 of 24] vs. 58% [14 of 24]). These data show that preoperative 11C-acetate PET/CT may be a promising approach for the evaluation of immune status and postoperative outcome of HCCs.

Serologic detection of regenerating protein I alpha by time-resolved fluoroimmunoassay and its clinical value in gastric cancer.

Regenerating protein I alpha (REG Iα) plays a key role in the progression of gastric cancer (GC). However, the clinical application value of serum REG Iα in GC remains largely unknown. Serum REG Iα levels were analyzed through time-resolved fluoroimmunoassay (TRFIA) in healthy controls (HCs) and patients with benign gastric disease (BGD) and GC. The REG Iα levels of patients with GC were significantly higher than those of HCs and patients with BGD (P < .0001). The REG Iα levels were higher in patients with GC with poor pathological differentiation type; tumor, node, and metastasis stages III-IV; deep tumor invasion (T3-T4); and distant metastasis (P < .05). The diagnostic efficiency of the combined REG Iα, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9(CA19-9) tests improved compared with that of the single-indicator test for the diagnosis of patients with GC. REG Iα-TRFIA may facilitate the ancillary diagnosis of GC and have a monitoring role for further progression of GC. It can also help elucidate the possible diagnostic role of serum REG Iα as a noninvasive tool.

Comparison of reconstruction techniques after pancreatoduodenectomy: A single-center retrospective cohort study.

There is controversy regarding which is the best reconstruction technique after the pancreatoduodenectomy. Currently, there are no studies comparing the three most frequent reconstruction techniques: Whipple + Roux-en-Y gastrojejunostomy (WRYGJ), pyloric-preserving + Billroth II (PPBII), and Whipple + BII (WBII). Between 2012 and March 2023, 246 patients underwent pancreaticoduodenectomy with the following type of reconstruction techniques: (1) WRYGJ: 40 patients; (2) PPBII: 118 patients; and (3) WBII: 88 patients. A retrospective comparative study among these groups was performed. No significant differences were found among the groups regarding duration of the surgery, the blood volume transfused, or caliber of the Wirsung duct. The size and types of tumors, the degree of differentiation and tumor invasion of the peripancreatic tissue, vascular and neural structures, and lymph nodes were similar among the groups. The rate of R0 resection was lower in WBII (62.5% [55/88]) than in WRYGJ (75% [30/40]) and PPBII (72% [85/118]), but statistically insignificant among the groups (p = 0.232). The incidences of relevant B/C postoperative pancreatic fistula (POPF) were similar among the groups: 7.5% (7/40) in WRYGJ, 17% (20/118) in PPBI, and 26.2% (23/88) in WBII (p = 0.292). In addition, the incidence of B/C delayed gastric emptying (DGE) was higher in WBII (27.3% [24/88]) than in WRYGJ (20% [8/40]) and PPBII (19.5% [23/118]) but statistically insignificance among the groups (p = 0.381). The incidence of medical and surgical complications, intensive care unit and hospital stays, morbimortality at 90 days, and 5-year survival were similar among the groups. Multivariate analysis revealed that POPF grade B/C was a risk factor for DGE grade B/C (odds ratio (OR) = 9.903, 95% confidence interval (CI) = 4.829-20.310; p < 0.001), and a <3-mm Wirsung duct was a risk factor for POPF (OR = 3.604, 95% CI = 1.791-7.254; p < 0.001). No technique was superior to the others. Only relevant POPF B/C was a risk factor for DGE B/C, and <3 mm Wirsung for a POPF.

Molecular mechanisms of transcription factor KLF4-mediated immune infiltration influencing lung adenocarcinoma invasion.

Lung adenocarcinoma (LUAD) is associated with an increasing incidence and mortality rate while existing treatment strategies continue to exhibit considerable limitation. Studies have demonstrated that upregulation of KLF4 gene inhibits LUAD progression, but its underlying mechanisms remain elusive. The present research explored roles and mechanisms of KLF4 and the NF-κB pathway in LUAD. Lentiviral vectors encoding KLF4 were constructed and transduced into H1299 and A549 cells to generate stable cell lines. These stable cell lines were then injected into BALB/c mice to establish a LUAD model. Subsequently, RNA sequencing, HE staining, immunohistochemistry, ELISA, Western blotting, and flow cytometry were employed to investigate the effects of KLF4 on tumor growth, invasion, immune cell infiltration, and related signaling pathways. Finally, dual-luciferase and in vivo mouse experiments were conducted to validate the molecular mechanisms. KLF4 significantly reduced tumor cell invasion while promoted tumor cell necrosis. Transcriptomic sequencing identified CXCR2 as a target gene and the NF-κB signaling pathway associated with immune infiltration regulation. KLF4 downregulated NF-κB2 and CXCR2 expression, concomitantly decreasing tumor cell invasiveness but increasing levels of CD4+ and CD8+ T cells and macrophages. NF-κB and CXCR2 play an important role in KLF4-mediated immune infiltration, thereby inhibiting tumor invasion and promoting tumor cell apoptosis in mice.

Safety and efficacy of endoscopic resection for gastric gastrointestinal stromal tumors: a retrospective cohort study

Background The aim of this study was to verify the safety and efficacy of endoscopic resection (ER) for gastric gastrointestinal stromal tumors (GISTs). Methods Among a consecutive series of resections for gastric GISTs performed in a single center, the outcomes of patients who had ER were compared to standard surgical resection (SR). Results In the cohort, 329 consecutive primary localized gastric GISTs patients (n, ER/SR = 251/78) were enrolled. Patients receiving ER were revealed to have preferable post-treatment outcomes, prolonged overall survival (OS) and disease-free survival (DFS). Tumor diameter, the only independent risk factor for a complicated post-operative course, was utilized for propensity score matching (PSM). In the PSM cohort, patients receiving ER and SR with similar tumor size (4.0 [2.7–4.5] cm) shared similar aggressiveness in terms of stomach layers of tumor origination and invasion, and modified National Institutes of Health (mNIH) risk criteria. Shorter operative time, fewer economic costs, and shorter post-operative stay were still observed in the ER group (ER vs. SR: 80 [49–120] vs. 120 [98–160] minutes, p < 0.001; 44 [38–51] vs. 60 [49–84] thousand Renminbi [kRMB], p < 0.001; 7.0 [6.0–8.0] vs. 8.5 [6.0–12] days, p = 0.018, respectively). No significant difference in OS and DFS was demonstrated in the PSM cohort. Conclusions ER is safe and effective, thus a feasible treatment option for indicated gastric GISTs patients with the advantage of faster recovery and lower economic costs.

The regulatory role of integrin in gastric cancer tumor microenvironment and drug resistance.

Gastric cancer (GC) remains a significant global health burden due to its high aggressiveness, early metastasis, and poor prognosis. Despite advances in chemotherapy and targeted therapies, drug resistance remains a major obstacle to improving patient outcomes. Integrins, a family of transmembrane receptors, play a pivotal role in mediating tumor growth, invasion, and drug resistance by interacting with the tumor microenvironment (TME) and regulating signaling pathways such as Wnt/β-catenin, FAK, and MAPK. This review highlights the critical functions of various integrin subunits (e.g., α5, αv, β1, β3, β6) in promoting GC progression and their involvement in chemoresistance mechanisms. Additionally, integrins modulate immune cell infiltration and stromal cell interactions within the TME, further complicating GC treatment. Emerging evidence suggests that targeting integrins, either through inhibitors or integrin-specific therapeutic strategies, holds potential in overcoming drug resistance and improving clinical outcomes. This review underscores the need for further exploration of integrins as therapeutic targets in GC and suggests promising avenues for integrin-based therapies in personalized medicine.

The concomitant anxiety and depression in patients with epilepsy caused by low-grade brain tumors

The aim of the study was to evaluate the concomitant psychiatric disorders of anxiety and depression in patients with epilepsy caused by low-grade brain tumors (LBTs). We retrospectively reviewed the clinical data of patients who underwent preoperative neuropsychological evaluations of anxiety and depression and subsequent epilepsy surgery for LBTs. The univariate and multivariate analyses were conducted to analyze the risk factors of the occurrence of anxiety and depression. Of the 107 patients included in the study, 42 patients (39.3%) were female, and 28 patients (26.2%) were children. The median age at surgery was 22 years (interquartile range [IQR]: 17–27 years old), the median age of seizure onset was 12 years (IQR: 6–18 years old), and the median duration of epilepsy was 84 months (IQR: 42–180 months). In total, 21 patients (19.6%) had psychiatric disorders of anxiety, and 26 patients (24.3%) had psychiatric disorders of depression. Through univariate and multivariate analysis, discordant (vs. concordant) interictal electroencephalogram (EEG) findings were found to be related to the presence of anxiety (P = 0.035, odds ratio [OR] = 3.35). Discordant (vs. concordant) ictal EEG findings (P = 0.015, OR = 4.44) and temporal location of tumor (P = 0.015, OR = 13.52) were found to be associated with the presence of depression. Psychiatric disorders of anxiety and/or depression could frequently occur in patients with epilepsy caused by LBTs. Thus, early screening and mental intervention are necessary, especially for those with discordant or wider epileptic discharges and temporal invasion of tumors.