Cancer Management and Research最新文献

Matrine and its derivatives, as multi-target natural alkaloids, exhibit synergistic antitumor effects through the regulation of core oncogenic pathways including Wnt/β-catenin, MAPK/ERK, and PI3K/AKT/mTOR. These compounds inhibit tumor proliferation by suppressing epithelial-mesenchymal transition (EMT), inducing programmed cell death (apoptosis, autophagy, and pyroptosis), and remodeling the tumor immune microenvironment. Preclinical studies demonstrate that third-generation derivatives (e.g.MT-26, YF-18) enhance therapeutic efficacy by targeting DNMT1/HDAC6 dual inhibition and activating the NLRP3/caspase-1 pyroptosis pathway, achieving tumor suppression rates of 60-78% in pancreatic and liver cancer patient-derived xenograft (PDX) models while overcoming chemotherapy resistance. However, preclinical-to-clinical translation faces challenges such as low bioavailability, off-target toxicity (e.g.hepatotoxicity via JNK/c-Jun activation), and tumor heterogeneity-driven resistance mechanisms (eg SLC7A11-mediated ferroptosis evasion); notably, no Phase I/II clinical trials for matrine or its derivatives in cancer therapy have been registered to date. Future research should prioritize the development of intelligent delivery systems (DNA origami nanorobots, magnetically guided micro/nano-swimmers), multi-omics-driven precision strategies (spatial metabolomics, single-cell epi-drugomics), and synthetic biology platforms (PROTAC bifunctional molecules, AI-assisted crystal screening). Integrating organ-on-chip technologies and real-world data analytics will accelerate the transformation of matrine-based compounds into next-generation intelligent anticancer agents, offering innovative solutions for comprehensive cancer management.

Port-site metastasis (PSM) is an infrequent and serious complication of laparoscopic treatment. The incidence of PSM is 0.16-2.3% of patients undergoing laparoscopic surgery for gynecologic malignancies. Depending on the place of origin of the malignant tumor, PSM appears on average the earliest after ovarian cancer treatment and the latest after vaginal cancer surgery. To date, several important risk factors have been identified. Hypotheses such as wound contamination, hematogenous and lymphatic spread, immune response and CO2 pneumoperitoneum have been formulated as possible agents influencing the occurrence of PSM. Overall survival (OS) is a particularly important issue from the standpoint of the person performing the procedure and the patient. OS may be influenced by the histological type of cancer, its origin in the body, the method of treatment, as well as the type of PSM and the time of its occurrence after the end of therapy. Patients with PSM require local or systemic treatment, as well as consideration of complementary therapy. There are theories indicating that appropriate preoperative management in patients with gynecological malignancies can prevent the occurrence of PSM. Despite enormous laparoscopy development over the last 20 years, a complication such as PSM still leaves many unknowns and therefore causes difficulties in therapeutic procedures. Each patient should be closely monitored before and after the laparoscopic procedure to exclude potential factors for the occurrence of PSM and its possible post-procedure diagnosis. Moreover, it is the responsibility of the person performing laparoscopy to accomplish the procedure as precisely as possible to minimize the risk of this complication. The main aim of the following review is to present the phenomenon of PSM in gynecologic oncology, its epidemiology, pathogenesis and possible consequences for the prognosis of the patient.

Background: Spontaneous rupture of hepatocellular carcinoma (srHCC) carries a high risk of peritoneal metastasis and poor prognosis. While hyperthermic intraperitoneal chemotherapy (HIPEC) is established for peritoneal metastases in other cancers, its prophylactic role after radical resection of srHCC remains undefined. This study evaluated the efficacy and safety of HIPEC in improving outcomes for srHCC patients post-hepatectomy.

Methods: In this retrospective study, 77 patients with srHCC undergoing hepatectomy (2016-2022) were categorized into the HR-HIPEC group (n=30) and the non-HIPEC group (n=47). Clinical features and survival data were analyzed.

Results: The HR-HIPEC group demonstrated significantly superior median overall survival (OS: 44 vs 35 months; P=0.027) and recurrence-free survival (RFS: 44 vs 25 months; P=0.007). The 3-year OS (73.85% vs 44.17%) and RFS (54.72% vs 24.47%) rates were also higher with HIPEC. Multivariate analysis identified HIPEC as an independent protective factor for both OS (HR=9.301, P<0.001) and RFS (HR=2.159, P=0.044). Postoperative recovery, morbidity, and mortality were comparable between groups. Subgroup analysis of HIPEC regimens (gemcitabine/cisplatin vs oxaliplatin/5-FU/folinic acid) revealed no significant differences in efficacy, though the latter was associated with transiently lower hemoglobin (P=0.006).

Conclusion: Prophylactic HIPEC is a safe and feasible adjunct to hepatectomy that significantly improves survival outcomes in srHCC patients without increasing perioperative risks. The choice between the two chemotherapy regimens studied did not affect efficacy, warranting further investigation to optimize protocols.

Purpose: Colorectal cancer (CRC) is a prevalent cancer worldwide, with metastasis significantly contributing to its high mortality and poor prognosis. This study focuses on the impact of Alkaline Phosphatase, Placental (ALPP) on epithelial-mesenchymal transition (EMT) in colorectal cancer cells and its role in the Wnt/β-catenin signaling pathway.

Patients and methods: Differential ALPP expression was first interrogated in metastatic versus non-metastatic CRC samples from The Cancer Genome Atlas (TCGA-CRC) cohort. Functional validation was subsequently performed in vitro with HT29 and HCT116 cell lines engineered for ALPP overexpression or CRISPR/Cas9-mediated knockdown. Proliferation, migration and invasion were quantified by CCK-8, wound-healing and Transwell assays; EMT and Wnt/β-catenin signaling were assessed by Western blot.

Results: Bioinformatics analysis revealed significantly different ALPP expression between metastatic and non-metastatic patients. In vitro experiments further revealed that ALPP overexpression drives proliferation, invasion, migration and, consequently, metastasis of HT29 and HCT116 colorectal cancer cells, whereas ALPP knockdown abolishes these EMT-dependent effects. Increased ALPP expression resulted in increased levels of N-Cadherin, Vimentin, and Snail proteins, along with a decrease in E-cadherin protein expression, in contrast to findings following ALPP knockdown. Furthermore, ALPP overexpression was also associated with Wnt/β-catenin signaling pathway activation.

Conclusion: ALPP was found to act as an oncogenic factor in colorectal cancer cell lines HT29 and HCT116, stimulating cell proliferation and facilitating EMT. Abnormal activation of the Wnt/β-catenin signaling pathway was also found to be linked to increased ALPP expression.

Ferroptosis refers to the regulatory cell death type with the typical feature of iron-dependent lipid peroxidation (LPO), which has been implicated in various aspects of cancer development and progression. Ferroptosis dysregulation can promote the occurrence, metastasis, and therapy resistance of gastric cancer (GC). Understanding the ferroptosis-related molecular mechanisms in GC progression could lead to novel therapeutic strategies that target this pathway. This review briefly introduces the mechanisms of ferroptosis and concludes that targeting ferroptosis can regulate the sensitivity of GC cells to chemotherapy resistance and immunotherapy. Natural plant extracts and traditional medicine play a key role in the treatment of GC by inducing ferroptosis through pathways such as activating p53 and inhibiting nuclear factor erythrocyte 2-related factor 2 (NRF2). Additionally, novel nanoparticle materials can be used as a drug carrier to promote ferroptosis while suppressing GC cell or gastric cancer stem cell (GCSC) growth, providing a novel direction for treating GC. It also summarizes other drugs such as 6-Thioguanine, Polymerase theta, levobupivacaine and clinical application drugs, which target ferroptosis, the effect of them in treating GC. This review highlights the potential of ferroptosis induction in GC treatment, providing new avenues for clinical intervention. Finally, this review looks forward to the translational prospects of targeting ferroptosis in the development of GC treatment, offering key insights for future research directions and therapeutic strategies.

Purpose: Baicalein, a natural flavonoid derived from the root of Scutellaria baicalensis, has demonstrated antitumor efficacy in several cancers. However, its effects on human mesothelioma remain largely unclear. This study evaluates the antitumor roles and mechanisms of baicalein in mesothelioma cell lines.

Materials and methods: Effects of baicalein on mesothelioma cells phenotypic changes were investigated by measuring cell proliferation, apoptosis, migration, invasion, and cell-cycle alterations. Bioinformatic methods were applied to predict the mechanisms by which baicalien mediated its antitumor roles in mesothelioma. Crucial signaling molecules among p53-FOXM1 signaling axis, including p53, FOXM1 and cyclin B1, were evaluated by immunoblotting in mesothelioma cells.

Results: Treatment with baicalein significantly inhibited mesothelioma cell viability in a dose-dependent manner, with 48 h IC₅₀ values of 48.9 µM for MESO257 and 53.2 µM for MESO924. Baicalein also markedly reduced cell migration and invasion, while inducing apoptosis in both cell lines. Mechanistically, baicalein suppressed the p53-FOXM1 signaling axis, decreasing FOXM1 and Cyclin B1 while increasing p53 expression. Furthermore, FOXM1 overexpression attenuated the antiproliferative, anti-migratory, anti-invasive and proapoptotic effects of baicalein.

Conclusion: Baicalein suppresses mesothelioma cell growth and invasion in vitro through modulation of the p53-FOXM1 signaling axis. These findings support its potential as a lead compound for further preclinical evaluation in mesothelioma.

Objective: Glutaryl-CoA dehydrogenase (GCDH) is a mitochondrial enzyme involved in lysine and tryptophan catabolism, yet its role in cancer metabolism remains poorly understood. This study aimed to investigate the function of GCDH in regulating glutamine metabolism and proliferation in breast cancer cells, and to elucidate its molecular mechanism via epigenetic modulation of glutaminase 1 (GLS1).

Methods: GCDH expression was silenced using siRNAs in human breast cancer cell lines MCF-7 and MDA-MB-231. Cell proliferation was assessed using CCK-8 and EdU assays. Glutamine metabolism was analyzed by quantifying intracellular levels of glutamine, glutamate, α-ketoglutarate (α-KG), and ATP. In vivo effects were evaluated using a xenograft model in BALB/c nude mice. Chromatin immunoprecipitation (ChIP), luciferase reporter assays, and Western blotting were performed to explore the epigenetic regulation of GLS1. Functional interaction between GCDH and GLS1 was further validated through overexpression and knockdown studies, and the requirement for GCDH's enzymatic activity was tested using a catalytically inactive mutant.

Results: GCDH knockdown significantly suppressed proliferation in MCF-7 and MDA-MB-231 cells (p<0.001), decreased EdU incorporation (p<0.01), and impaired glutamine metabolism, as indicated by elevated intracellular glutamine and reduced levels of glutamate, α-KG, and ATP (all p<0.05). In vivo, GCDH depletion led to reduced tumor growth and weight (p<0.001), with altered metabolic profiles consistent with impaired glutaminolysis (decreased α-KG, p<0.05). Mechanistically, GCDH silencing reduced global and GLS1 promoter-specific H3K27 crotonylation (p<0.01), suppressing GLS1 transcriptional activity (p<0.001). Overexpression of GLS1 reversed the metabolic and proliferative deficits induced by GCDH knockdown. Furthermore, wild-type GCDH overexpression, but not a catalytically inactive mutant, partially restored glutamate production and ATP levels in GLS1-deficient cells (p<0.05), indicating a functional interplay that depends on GCDH's enzymatic activity.

Conclusion: GCDH promotes breast cancer cell proliferation and metabolic activity by enhancing glutaminolysis through epigenetic upregulation of GLS1 via histone crotonylation. Critically, this novel metabolic-epigenetic axis requires the catalytic function of GCDH. These findings not only reveal a novel metabolic-epigenetic axis driven by a specific mitochondrial enzyme but also suggest GCDH as a potential therapeutic target in breast cancer.

Purpose: Vitamin K1 (VK1) has been proved to have anticancer properties in various cancer cells. However, little is known about the effects of VK1 on hematologic malignancies. The aim of this study was to evaluate the cytotoxic effects of VK1 on Jurkat T Lymphocyte Leukemia Cells (Jurkat T cells), as well as to investigate the changes in gene expression.

Methods: Jurkat T cells and normal human peripheral blood mononuclear cells (PBMCs) were treated with VK1 at different concentrations, and the cell viabilities were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was detected by Annexin V-FITC cell apoptosis detection kit and the cell cycle was determined by PI staining and flow cytometric analysis. Differentially expressed genes (DEGs) of Jurkat T cells induced by VK1 were analyzed by RNA sequencing. The mRNA expression of HMGCR and HMGCS1 were further verified by real-time RT-qPCR.

Results: VK1 showed an obviously antiproliferative effect on Jurkat T cells but no any effects on normal human PBMCs. VK1 induced Jurkat T cells apoptosis and cell cycle arrest at G0/G1 phase. A total of 21 down-regulated and 34 up-regulated genes were identified by transcriptome analysis. We selected HMGCR and HMGCS1 genes among the significantly up-regulated genes for further RT-qPCR analyzation. It was confirmed that VK1 up-regulated the mRNA expression of HMGCR and HMGCS1.

Conclusion: VK1 has cytotoxic effects and transcriptional regulation of multiple genes on Jurkat T cells. The genes of HMGCR and HMGCS1 related pathways may play roles in this process.

Aim of the study: To analyze the chemical components of BSCO, evaluate its effects on lung cancer through vivo and vitro experiments, reveal its underlying mechanism in a rat model of LC.

Methods: Ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was used to identify components of BSCO. A Lewis lung cancer model was established in mice to evaluate the effects of BSCO by observing tissue morphology, whole animal imaging, and determination of serum biochemical indicators. The effects of BSCO on Lewis cancer cells in vitro were assessed using a CCK-8 cell proliferation assay. Network pharmacology and transcriptomics analysis was used to predict their targets and signaling pathways associated with lung cancer. The mRNA expressions of target genes were measured by RT-qPCR.

Results: Twenty major chemical components of BSCO were identified. BSCO effectively inhibited tumor growth in the Lewis lung cancer mouse model and normalized serum markers of cancer to varying degrees. The IC₅₀ of BSCO on Lewis cell proliferation was 173 mg/mL. Low- and high-dose BSCO-containing drug serum inhibited proliferation of Lewis cells after 24 and 48 h incubation. Integrated network pharmacology and transcriptomic analyses suggest that BSCO may exert anti-tumor effects through the PI3K-Akt signaling pathway, with TP53, IL6, CDKN1A, and KIT identified as potential key targets within this pathway. The reliability of the transcriptomic results was confirmed by verifying some lung cancer-related genes through RT-qPCR. BSCO was evaluated against model control and cyclophosphamide. A key follow-up step will be to perform protein-level validation, which confirms the observed transcriptomic signals.

Conclusion: BSCO significantly inhibited lung cancer growth in vitro and in vivo. Network pharmacology and transcriptomics suggested that its anti-cancer effects might involve the PI3K-Akt signaling pathway, TP53, IL6, CDKN1A, and KIT may be its key targets.

Skin metastasis, a rare occurrence in cervical cancer, typically signifies advanced systemic disease with a poor prognosis. This case report presents a 55-year-old female with recurrent cervical adenocarcinoma, intrapulmonary metastasis, and metachronous mucinous ovarian cancer who developed skin metastasis. The patient presented with skin-colored and hyperpigmented plaques and papules on the lower abdomen. The histopathological examination of the skin lesion from the patient in this case report revealed subepithelial tumor masses composed of round to oval cells growing hyperplastically in compact clusters, with some forming glandular structures. The nuclei exhibited pleomorphism, ranging from hyperchromatic to vesicular, with clear nucleoli, and mitotic figures were observed. The fibrocollagenous stroma appeared partly edematous, while the skin adnexa, including the sweat and sebaceous glands, remained intact. Immunohistochemical staining for p16 in the skin lesion showed strong positivity in stromal tumor cell infiltrates and negativity in the papillary epithelium, supporting a metastatic origin from cervical adenocarcinoma, confirming the diagnosis of skin metastasis from adenocarcinoma. She was treated with three cycles of paclitaxel and carboplatin chemotherapy, resulting in thinning and a reduction in the size and number of plaques and papules. Despite the positive therapeutic response, the overall prognosis remains poor, and she passed away 16 months after the initial appearance of skin metastasis. This case underscores the importance of routine skin examination in cervical cancer patients, as skin metastasis often correlates with advanced disease and distant organ involvement. Early biopsy and prompt treatment may enhance progression-free survival in such cases.