Neoplasma[JOURNAL]
Sun
200 papers
Synergistic effects of histone deacetylase inhibitor chidamide and BCL-2 inhibitor venetoclax in activating the p53 pathway in diffuse large B-cell lymphoma.
Song Z, Song Z, Ren L … +3 more , Han X, Zhang X, Wen S
Neoplasma · 2025 Aug · PMID 40958520 · Publisher ↗
This study aimed to evaluate synergistic effects and molecular mechanisms of the histone deacetylase inhibitor chidamide combined with the BCL-2 inhibitor venetoclax in diffuse large B-cell lymphoma (DLBCL) cell lines. H...
This study aimed to evaluate synergistic effects and molecular mechanisms of the histone deacetylase inhibitor chidamide combined with the BCL-2 inhibitor venetoclax in diffuse large B-cell lymphoma (DLBCL) cell lines. Human DLBCL cell lines (U2932, SUDHL-4) were cultured in vitro and treated with chidamide and venetoclax. Cell proliferation inhibition rates were measured using the CCK-8 assay, and IC50 values were calculated. Cells were also treated with a 5:1 combination of chidamide and venetoclax, along with p53 or p21 siRNA. Cell viability, HDAC activity, apoptosis, cell cycle, the amount of p53 and p21 proteins, and BCL-2-BIM binding were analyzed via CCK-8, enzyme activity assays, the Caspase 3/7 Activity Apoptosis Assay Kit, flow cytometry, RT-qPCR, western blot, and co-IP. The binding of p53 and p21 was verified by dual-luciferase reporter assay and chromatin immunoprecipitation. Chidamide and venetoclax exhibited dose- and time-dependent anti-proliferative effects in U2932 and SUDHL-4 cells, with IC50 values of 3.54 μM (chidamide) and 0.67 μM (venetoclax) in the SUDHL-4 cell line and 5.6 μM (chidamide) and 0.91 μM (venetoclax) in the U2932 cell line. Combination treatment significantly enhanced HDAC inhibition, histone H3/H4 acetylation, and p53 expression, leading to increased cell apoptosis. p53 knockdown partially reversed these effects and increased BCL-2/BIM complex formation. The combination also upregulated p53 expression to increase p21 expression, inducing G1/S phase arrest, which was partially reversed by p21 knockdown. To conclude, the chidamide-venetoclax combination synergistically activates the p53-p21 signaling pathway, leading to cell cycle arrest and apoptosis, representing a potential therapeutic strategy for DLBCL.
Temozolomide and anlotinib as second-line therapy for non-small cell lung cancer patients with brain metastases: a retrospective cohort study.
Liu K, Li B, Xiang Z … +2 more , Tang J, Li X
Neoplasma · 2025 Aug · PMID 40693542 · Publisher ↗
Brain metastases (BM) are a common and challenging complication of advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of the combination of temozolomide (TMZ) and anlotinib...
Brain metastases (BM) are a common and challenging complication of advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of the combination of temozolomide (TMZ) and anlotinib as a second-line treatment in advanced NSCLC patients with BM. Clinical data of advanced NSCLC patients with BM between January 2020 and December 2023 were retrospectively reviewed and analyzed. All patients received TMZ combined with anlotinib as a second-line treatment. The primary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). A total of 52 patients were enrolled, with 20 females and 32 males. The median PFS and OS were 5.0 months and 10.0 months. The ORR and DCR were 25% and 65%, respectively. Subgroup analysis demonstrated that patients who developed AEs such as hypertension, proteinuria, and hand-foot syndrome, as well as those with a favorable diagnosis-specified graded prognosis assessment score, had better efficacy outcomes, indicating these features may help to identify the priority population for this regimen. Common AEs, including hematological toxicity, fatigue, and hypertension, were generally manageable with dose adjustments and supportive care. TMZ combined with anlotinib could be a safe and effective second-line treatment option for advanced NSCLC patients with BM. Prospective trials are warranted to confirm these findings and optimize the treatment strategy.
High glycolysis phenotype influences malignant progression and poor prognosis of gastric cancer through the PI3K/AKT pathway.
Liu S, Shen G, Zhou X … +6 more , Wang G, Liu H, Cao Y, Sun L, Shu X, Ran Y
Neoplasma · 2025 Aug · PMID 40693541 · Publisher ↗
Gastric cancer (GC) is a prevalent gastrointestinal malignancy, with metabolic reprogramming, particularly glycolysis, playing a critical role in cancer cell stemness. However, the interaction between glycolysis and GC p...
Gastric cancer (GC) is a prevalent gastrointestinal malignancy, with metabolic reprogramming, particularly glycolysis, playing a critical role in cancer cell stemness. However, the interaction between glycolysis and GC prognosis, along with its underlying mechanisms, remains poorly understood. This study aimed to systematically analyze the prognostic significance of glycolysis in GC and explore its functional impact. A glycolysis-related gene score was constructed using bioinformatics to assess glycolysis levels based on differentially expressed genes between GC and normal tissues. A nomogram model was developed to predict clinical prognosis, and the functional phenotypes of GC cell lines cultured under high and low glucose conditions were evaluated using metabolite detection and extracellular acidification rate (ECAR) measurements. Enrichment analyses identified key signaling pathways, which were further validated by western blot. Results showed that elevated glycolysis was associated with larger tumor size and poorer prognosis in GC patients. The nomogram demonstrated strong predictive accuracy. High glucose culture promoted glucose consumption, lactate production, ATP generation, and ECAR, enhancing epithelial-mesenchymal transition and malignant progression via the PI3K/AKT pathway. In conclusion, high glycolysis is linked to poor prognosis in GC and drives metastasis and stemness through the PI3K/AKT signaling pathway, highlighting its potential as a prognostic marker and therapeutic target.
ANLN knockdown inhibits nasopharyngeal carcinoma proliferation and is associated with impaired ribosome biogenesis.
Zhu Z, Fu L, Bai X … +4 more , Zhang W, Liu S, Min H, Liu Y
Neoplasma · 2025 Aug · PMID 40693540 · Publisher ↗
Anillin (ANLN), an actin-binding protein, has been implicated in tumorigenesis across various cancers; however, its role in nasopharyngeal carcinoma (NPC) remains largely undefined. In this study, we analyzed ANLN expres...
Anillin (ANLN), an actin-binding protein, has been implicated in tumorigenesis across various cancers; however, its role in nasopharyngeal carcinoma (NPC) remains largely undefined. In this study, we analyzed ANLN expression using TCGA, CPTAC, and GEO datasets, and confirmed its overexpression in NPC tissues and cell lines through qRT-PCR, western blotting, and immunohistochemistry. High ANLN expression correlated with advanced clinical stage and poor overall survival. Functional assays, including CCK-8 and colony formation, demonstrated that ANLN knockdown suppressed NPC cell proliferation in vitro, while xenograft models confirmed reduced tumor growth in vivo. RNA sequencing and gene set enrichment analysis revealed that ANLN knockdown was associated with downregulation of ribosome biogenesis pathways. Puromycin incorporation assays and transmission electron microscopy further supported impaired protein synthesis and nucleolar disruption following ANLN depletion. These findings suggest that ANLN promotes NPC progression by maintaining ribosome biogenesis and protein synthesis and may serve as a novel prognostic biomarker and therapeutic target.
STING expression in colorectal cancer: prognostic role and immune microenvironment link via mIHC.
Zhang M, Song H, Zhou X … +3 more , Zhou C, Xu Y, Li S
Neoplasma · 2025 Jun · PMID 40635509 · Publisher ↗
Colorectal cancer (CRC) is a malignant tumor originating in the mucosal epithelium of the colon or rectum and is among the most common cancers of the digestive system. Now it is the fourth deadliest cancer in the world....
Colorectal cancer (CRC) is a malignant tumor originating in the mucosal epithelium of the colon or rectum and is among the most common cancers of the digestive system. Now it is the fourth deadliest cancer in the world. Stimulator of Interferon Genes (STING) is a dimeric transmembrane protein on the endoplasmic reticulum membrane that induces the secretion of type I interferons and pro-inflammatory cytokines and is triggered by the cell membrane DNA of pathogens and hosts. It is widely expressed in immune cells (such as dendritic cells, macrophages) and some tumor cells, and has been shown to play a crucial role in the development of several tumors. However, issues such as the expression of STING in CRC and patient prognosis remain to be further elucidated. We investigated the expression of STING (in CRC tumor cells) and immune markers (CD3, CD4, CD8, CD56, CD163) in 86 CRC patients by tissue microarray using multicolor immunohistochemistry. Subsequently, the effect of STING on the tumor immune microenvironment was further explored. Finally, we analyzed the clinical significance of STING in CRC patients. We found elevated STING expression in tumor cells from CRC patients, which correlated with overall patient survival. High STING levels were associated with suppression of lymph node metastasis and reduction of CD163 tumor-associated macrophages. In contrast, upregulation of STING promoted infiltration of CD3+ T lymphocytes and CD8 lymphocyte subtype in the tumor microenvironment. Our study demonstrated that changes in STING expression in cancer cells in the tumor immune microenvironment have clinical significance and regulatory roles. STING-related functional mechanisms can be considered as therapeutic targets for CRC, which provides a theoretical basis for the subsequent clinical application of STING agonists.
Stereotactic body radiation therapy for liver metastases and primary liver tumors: treatment results and toxicity.
Dobnikar N, Secerov Ermenc A, Grabec D … +6 more , Jeromen Peressutti A, Korosec P, Zager Marcius V, Boc N, Ratosa I, Oblak I
Neoplasma · 2025 Jun · PMID 40635508 · Publisher ↗
The aim of our research was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for the liver in all patients diagnosed with either primary liver tumor or metastases from other primary malignan...
The aim of our research was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for the liver in all patients diagnosed with either primary liver tumor or metastases from other primary malignancies since its initial application at a single institution. A retrospective analysis of the prospective designed registry included 105 patients with 133 liver metastases or primary tumors treated with SBRT from the introduction of the technique in March 2018 until November 2023. The main objectives of the study were to evaluate treatment toxicity, disease control, and survival rates. At a median follow-up of 24 months, a complete response to treatment was achieved in 86.7% of patients. During irradiation, only one patient experienced grade 3 abdominal discomfort, while the other 34.3% of patients experienced only mild acute adverse events (AEs), the majority of which were nausea. After completion of SBRT, 36.2% of patients reported AEs, but only grade 1 and 2 toxicity was observed. The one-, two-, and five-year LC rates were 89.2%, 84.9%, and 84.9%, respectively. DFS rates were 54.7%, 42.9%, and 25.8%; DSS rates were 94.9%, 81.1%, and 46.8%; and OS rates at one, two, and five years were 93.1%, 79.6%, and 43.2%, respectively. In the multivariate analysis, only the number of lesions presented independent prognostic value. In conclusion, SBRT offers effective disease control and survival rates with minimal toxicity, side by side with surgical options as a curative treatment for liver tumors.
RAN contributes to bortezomib resistance in multiple myeloma via regulating the Wnt/PCP pathway.
Li L, Xu L
Neoplasma · 2025 Jun · PMID 40635507 · Publisher ↗
Previous studies have shown that Ras-Related Nuclear Protein (RAN), a member of the RAS superfamily, is a small GTPase and an important oncogene in several cancers. However, its role in multiple myeloma (MM) and its pote...
Previous studies have shown that Ras-Related Nuclear Protein (RAN), a member of the RAS superfamily, is a small GTPase and an important oncogene in several cancers. However, its role in multiple myeloma (MM) and its potential contribution to drug resistance remain undetermined. Bioinformatics was employed to analyze differentially expressed genes in MM samples. RT-qPCR and western blotting were utilized for protein transcription and expression analysis. The CCK-8 assay was adopted to evaluate cell proliferation, and in vivo animal experiments were conducted to validate the results. The findings reveal that RAN represents one of the most significantly aberrant genes in MM, with its expression significantly elevated in both MM tissues and cells. Genetic manipulation experiments demonstrated that RAN promotes MM cell proliferation by activating the Wnt/PCP pathway. Concurrently, RAN governs the response of MM cells to the anti-cancer drug bortezomib (BTZ). Knockdown of RAN leads to increased sensitivity to BTZ. Mechanistic studies indicate that RAN influences drug response by regulating the activation of the JNK/c-Jun axis, thereby affecting the therapeutic response of MM cells. In summary, the upregulated expression of RAN in MM leads to BTZ resistance via activation of the Wnt/PCP pathway, potentially serving as a novel therapeutic target for MM.
Adjuvant treatment efficacy in esophageal adenocarcinoma patients receiving neoadjuvant therapy and esophagectomy.
Xu M, Xu F, Luo J … +2 more , Zhang C, Shen Y
Neoplasma · 2025 Jun · PMID 40635506 · Publisher ↗
The application of adjuvant therapy following neoadjuvant treatment and subsequent esophagectomy remains a subject of debate due to the limited availability of comprehensive studies. This study aims to evaluate the role...
The application of adjuvant therapy following neoadjuvant treatment and subsequent esophagectomy remains a subject of debate due to the limited availability of comprehensive studies. This study aims to evaluate the role of adjuvant therapy in patients with esophageal adenocarcinoma (EAC) who have undergone neoadjuvant therapy and esophagectomy, thereby offering evidence-based guidance for clinical decision-making. Patients diagnosed with EAC and treated with neoadjuvant therapy followed by surgical intervention were enrolled in our study. The data for patients in the training cohort were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. To validate the findings, new patient cohorts were utilized. A total of 3,445 patients with EAC were identified from the SEER database based on the established eligibility criteria. The analysis revealed no significant differences between the adjuvant therapy group and the non-adjuvant therapy group in terms of 5-year overall survival, with rates of 35.7% and 37.2%, respectively (p=0.920), nor in 5-year cancer-specific survival, with rates of 39.5% and 43.2%, respectively (p=0.520). Additionally, 130 patients were identified from the Affiliated Jinling Hospital of Nanjing University's Medical School. In this cohort, findings indicated that patients receiving adjuvant therapy demonstrated improved overall survival compared to those not receiving such therapy (p=0.031). Leveraging the SEER database, our study demonstrated that adjuvant therapy did not confer a survival advantage for patients with EAC following neoadjuvant therapy and surgery. In contrast, data analysis from the Affiliated Jinling Hospital, Medical School of Nanjing University in China, indicated that EAC patients might indeed benefit from adjuvant therapy after undergoing neoadjuvant treatment and esophagectomy.
Factors influencing survival after allogeneic stem cell transplantation for hematologic malignancies in adult patients: A retrospective cohort study.
Oravcova I, Rusinakova Z, Cingelova S … +9 more , Ladicka M, Mikuskova E, Vranovsky A, Demitrovicova L, Kasperova B, Petrikova L, Slobodova A, Vasickova R, Drgona L
Neoplasma · 2025 Jun · PMID 40386922 · Publisher ↗
Allogeneic stem cell transplantation (alloSCT) remains the established main treatment option with curative potential for many hematologic malignancies. We conducted a retrospective analysis of 104 adult patients who unde...
Allogeneic stem cell transplantation (alloSCT) remains the established main treatment option with curative potential for many hematologic malignancies. We conducted a retrospective analysis of 104 adult patients who underwent alloSCT between March 2013 and November 2023. Kaplan-Meier survival analysis, the chi-square test, and Cox regression models were used to identify risk factors and outcomes. The median follow-up of the cohort was 19 (0.3-128.1) months. The median age of the recipients was 49 (19-65) years, and 57 (54.8%) recipients were males. Ninety (86.5%) patients had a matched sibling, and 14 (13.5%) had a haploidentical donor. According to the multivariable analysis, a body mass index (BMI) ≥30 kg/m2 (p=0.02) and status without chronic graft-versus-host disease (cGVHD) (p=0.04) were significantly associated with worse overall survival (OS). A BMI ≥30 kg/m2 was also predictive of worse relapse-free survival (p=0.01). The cumulative incidence rates of nonrelapse mortality (NRM) and relapse mortality (RM) at 1 year were 8.5% (95% CI: 4.3-16.5%) and 26.7% (95% CI: 19.1-37.4%), respectively. Patients without cGVHD had significantly higher RM than patients with cGVHD (p<0.001), whereas patients with cGVHD had significantly higher NRM (p=0.01). Patients with a BMI ≥30 kg/m2 had significantly more posttransplant fatal events (p<0.001). Our analysis revealed that a BMI ≥30 kg/m2 and a status without cGVHD were significantly associated with worse OS. NRM was higher in patients with cGVHD, whereas patients without cGVHD died mostly from relapses.
Survival benefit of early radium-223 dichloride therapy in castration-resistant prostate cancer patients with osteoblastic bone metastases.
Takacsova E, Bartovic M, Ivancik J … +1 more , Waczulikova I
Neoplasma · 2025 Jun · PMID 40386921 · Publisher ↗
The aim of the retrospective cohort study was to evaluate the overall survival of patients with castration-resistant prostate cancer and osteoblastic bone metastases without visceral metastases treated with 223Radium dic...
The aim of the retrospective cohort study was to evaluate the overall survival of patients with castration-resistant prostate cancer and osteoblastic bone metastases without visceral metastases treated with 223Radium dichloride (223Ra). The cohort included 55 patients aged 48 to 86, with a median age of 71. Overall survival from the first administered cycle (from 7/2015 to 7/2019) was evaluated in 10/2024. The median overall survival was, despite a smaller cohort, 16.27 months (CI: 11.87-20.98 months), comparable to other large real-world studies. Asymptomatic or mildly symptomatic patients with good performance status (ECOG 0-1) at the start of therapy had a significantly higher median survival than more symptomatic patients with ECOG 2 and 3 (22.42 vs. 8.06 and 3.28 months). The number of completed cycles of 223Ra was inversely proportional to the patients' performance status (ECOG) - Kendall's Tau-c = -0.625; p<0.0001. Previous treatment with chemotherapy (41.2 % of patients) was associated with significantly worse survival on multivariable analysis. A decrease of serum PSA by more than 50% (12.7% of patients) was significantly associated with longer survival (31 months; p=0.0043). Severe (Grade 3) anemia, leukopenia, and thrombocytopenia occurred in only 9.1%, 3.6%, and 3.6% of patients. Earlier indication of 223Ra dichloride therapy in asymptomatic or mildly symptomatic patients with good performance status (ECOG 0-1) and without prior chemotherapy improved survival in our cohort. The decrease in serum PSA during treatment was a good prognostic factor associated with longer survival.
WTAP is a promising diagnosis and treatment biomarker that inhibits the proliferation and invasion of melanoma cells.
Lu H, Zhang Y, Li J … +5 more , Lou D, Li L, Liang Y, Li J, Liu Y
Neoplasma · 2025 Jun · PMID 40386920 · Publisher ↗
Wilms' tumor 1-associating protein (WTAP) is ubiquitously expressed in many tissues and plays an important role in physiological processes and tumor development. Here, we investigated the specific biological role and und...
Wilms' tumor 1-associating protein (WTAP) is ubiquitously expressed in many tissues and plays an important role in physiological processes and tumor development. Here, we investigated the specific biological role and underlying mechanism of WTAP in melanoma. We determined the expression of WTAP and its correlation with clinicopathological features in paraffin-embedded tissues. We investigated the effects of WTAP on melanoma cells via a CCK-8 assay, a colony formation assay, an EdU assay, a Transwell assay, and subcutaneous xenograft experiments. We then applied RNA sequencing to further screen candidate targets, and NT5E was selected as the downstream gene of WTAP. Finally, a series of rescue assays, together with nucleotidase assays and ELISA, were adopted to confirm the function of NT5E in melanoma progression. We demonstrated that WTAP expression was downregulated in melanoma, which was associated with a poor prognosis, and that WTAP expression served as an independent predictor of melanoma survival. Functionally, WTAP hindered the proliferation, growth, migration, and invasion of melanoma cells. Furthermore, NT5E was identified as the downstream effector of WTAP and was subsequently found to rescue the increased proliferation, migration, and invasion of melanoma cells induced by WTAP deficiency. Moreover, knockdown of WTAP increased the expression of NT5E, MMP2, and N-cadherin, and simultaneous transfection with siNT5E reversed the increased expression of MMP2 and N-cadherin. Moreover, increased NT5E expression caused by forced WTAP inhibition in melanoma promoted the hydrolysis of AMP to produce more adenosine and further abrogated the secretion of IFN-γ by PBMCs. We found that WTAP expression is significantly downregulated and restrains the progression of melanoma via the downstream effects of NT5E on immunosuppression and molecular adhesion. This study revealed that WTAP plays a crucial inhibitory role in melanoma oncogenesis and highlighted WTAP as a potential novel diagnosis and therapeutic target for melanoma.
Metformin for recurrent colorectal polyp or adenoma prevention after polypectomy in patients without diabetes mellitus: a prospective study.
Wang W, Luo B, Wang Z … +5 more , Zhang J, Ye Z, He X, Li D, Sun D
Neoplasma · 2025 Apr · PMID 40353629 · Publisher ↗
To reduce the burden of colorectal cancer (CRC), the chemopreventive effects of 1-year metformin on polyps or adenoma recurrence in patients without diabetes mellitus (DM) who underwent polypectomy were evaluated. Patien...
To reduce the burden of colorectal cancer (CRC), the chemopreventive effects of 1-year metformin on polyps or adenoma recurrence in patients without diabetes mellitus (DM) who underwent polypectomy were evaluated. Patients without DM aged between 40 and 70 years old, with no polyp or adenoma after polypectomy, were randomly assigned to the control (no intervention), low-dose (500 mg/day), or high-dose (1,000 mg/day) metformin groups in a 1:1:1 ratio. After the 1-year intervention, the numbers of polyps and adenomas were measured and recorded, then resected. Plasma lipid and blood glucose were measured at baseline and 1-year follow-up. Data from the three groups were compared statistically. A total of 272 patients were enrolled in the analysis. In the control group, 48.9% of patients had adenoma recurrence, which was significantly higher than those in the low-dose (30.8%, p=0.012) and the high-dose (29.9%, p=0.009) metformin group. For the number of recurrent adenomas per subject, the difference between the control and the high-dose metformin groups was significant (0.86±1.09 vs. 0.47±0.83, p=0.020). No significant difference among the three groups and between baseline and 1-year follow-up was found in the lipid and glucose parameters. In conclusion, 1-year metformin use reduced the prevalence of recurrent adenoma significantly in patients without DM after polypectomy and may not be related to lipid and glucose metabolism.
EIF4E promotes gefitinib resistance in non-small cell lung cancer by activating the Wnt/β-catenin pathway.
Zhang B, Zhu J, Jin Z … +4 more , Liang J, Wang Z, Hu Q, Xia L
Neoplasma · 2025 Apr · PMID 40353628 · Publisher ↗
Tyrosine kinase inhibitors (TKIs) like gefitinib, which target the epidermal growth factor receptor (EGFR), show considerable therapeutic effectiveness in non-small cell lung cancer (NSCLC) with EGFR-activating mutations...
Tyrosine kinase inhibitors (TKIs) like gefitinib, which target the epidermal growth factor receptor (EGFR), show considerable therapeutic effectiveness in non-small cell lung cancer (NSCLC) with EGFR-activating mutations. Nevertheless, the resistance that develops against EGFR-TKIs diminishes their therapeutic impact in clinical settings. This investigation focused on the impact of eukaryotic translation initiation factor 4E (eIF4E) on gefitinib resistance in NSCLC. Using the CCK-8 assay, the influence of different gefitinib concentrations on cell proliferation was examined. eIF4E and EGFR expressions were verified by qRT-PCR and/or western blotting in NSCLC cell lines. Moreover, the effects of eIF4E knockdown in gefitinib-treated PC9/GR cells were detected by CCK-8, flow cytometry, colony formation assays, and xenograft tumor model. eIF4E expression was remarkably upregulated in the gefitinib-resistant PC9/GR cells. Moreover, the expression levels of eIF4E in NSCLC cell lines exhibited a dose-dependent increase following gefitinib administration. The function assays demonstrated that reducing eIF4E levels hindered the proliferation of PC9/GR cells and enhanced the apoptosis-inducing effects of gefitinib both in vitro and in vivo, and also had an inhibitory action on the Wnt/β-catenin pathway. Taken together, these results suggested that eIF4E confers gefitinib resistance in NSCLC by regulating the Wnt/β-catenin pathway. Therefore, eIF4E is a possible therapeutic target for improving therapeutic action in NSCLC patients who have developed resistance to gefitinib.
IL4I1 knockdown inhibits the epithelial-mesenchymal transition process in glioma via downregulation of the JAK2/STAT3 signaling pathway.
Zhuo J, Wang T, Lu T … +4 more , Li X, Yu Z, Cui G, Shen H
Neoplasma · 2025 Apr · PMID 40353627 · Publisher ↗
Gliomas are primary intracranial tumors that cause considerable morbidity and mortality. The effect of interleukin 4-induced gene-1 (IL4I1) on the progression of various diseases has been demonstrated to be significant....
Gliomas are primary intracranial tumors that cause considerable morbidity and mortality. The effect of interleukin 4-induced gene-1 (IL4I1) on the progression of various diseases has been demonstrated to be significant. However, the specific molecular mechanisms of how IL4I1 contributes to the progression and the epithelial-mesenchymal transition (EMT) process of glioma remain inadequately elucidated. IL4I1 expression in glioma was assessed using public datasets and immunohistochemistry. In in vitro experiments, IL4I1 expression was quantified through real-time quantitative PCR and western blotting. The effects of IL4I1 knockdown on the malignant phenotypes of glioma cells were investigated through in vitro studies. The evaluation of biomarkers associated with EMT and the Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway was conducted using western blotting and immunofluorescence assays after IL4I1 knockdown. A xenograft tumor model was established to validate the influence of IL4I1 knockdown in glioma progression. The results revealed that high expression of IL4I1 is linked to an unfavorable prognosis in human gliomas. IL4I1 knockdown effectively impeded the malignant phenotypes of glioma cells. IL4I1 knockdown induced EMT reversal, characterized by alterations in the expression levels and localization of EMT-related biomarkers. This reversal is partially mediated through the JAK2/STAT3 signaling pathway. The results of in vivo experiments confirmed that IL4I1 knockdown effectively suppressed glioma growth. Our research demonstrates that IL4I1 knockdown reverses the EMT process via JAK2/STAT3 signaling pathway and suppresses the malignant phenotypes of glioma, thereby highlighting its potential as both a prognostic marker and therapeutic target for glioma.
KLHL7 enhances cell viability and cell cycle progression in glioma via glutamine metabolism by activating the β-catenin signaling pathway.
Liu R, Cheng X, Wang P … +5 more , Xia X, Li G, Zhang F, Han C, Yao S
Neoplasma · 2025 Apr · PMID 40353626 · Publisher ↗
Kelch-like family member 7 (KLHL7) is associated with cancer development and occurrence, but its role and mechanism in the malignant progression of gliomas remain poorly understood. This study aimed to investigate the re...
Kelch-like family member 7 (KLHL7) is associated with cancer development and occurrence, but its role and mechanism in the malignant progression of gliomas remain poorly understood. This study aimed to investigate the regulatory effects and mechanisms of KLHL7 on cell cycle and glutamine metabolism in glioma. Glioma cell lines A172 and U87 and a xenograft mouse model were used to analyze the function of KLHL7 in vitro and in vivo, respectively. Gene expression levels and protein amounts were assessed by quantitative reverse-transcription polymerase chain reaction and western blotting, respectively. Cell viability was assessed using the CCK-8 assay, and the cell cycle was analyzed via flow cytometry. The glutamine content was measured using a biochemical assay. The level of KLHL7 was upregulated in patients with glioma. KLHL7 knockdown reduced cell viability, inhibited cell cycle progression, and decreased the glutamine content in A172 cells. KLHL7 silencing inhibited tumor growth in vivo. Furthermore, KLHL7 overexpression enhanced cell viability, cell cycle progression, and glutamine metabolism and activated the β-catenin signaling pathway in U87 cells. These findings indicate that KLHL7 promotes the malignant progression of glioma via the β-catenin signaling pathway and may serve as a biomolecule for the clinical prediction and treatment of the disease.
Clinical experience and safety of venetoclax in the treatment of patients with chronic lymphocytic leukemia - real-world data from a hemato-oncology center.
Holasová J, Wild A, Hrubiško M
Neoplasma · 2025 Apr · PMID 40353625 · Publisher ↗
The treatment of patients with CLL has undergone significant changes in recent years. Standard chemoimmunotherapy is changing to targeted inhibition with modern drugs. The listed drugs have better efficacy and significan...
The treatment of patients with CLL has undergone significant changes in recent years. Standard chemoimmunotherapy is changing to targeted inhibition with modern drugs. The listed drugs have better efficacy and significantly improve the overall survival of patients according to registry clinical studies. In a retrospective analysis, we evaluated 43 patients with CLL who underwent venetoclax treatment at the Hematology Department, University Hospital and Polyclinic F. D. Roosevelt Banská Bystrica, Slovakia (FNsP FDR BB) in 2019-2024. The aim of this work was to evaluate retrospectively the efficacy and safety of venetoclax in the treatment of patients with CLL. The median age of patients at the time of initiation of venetoclax treatment was 58 years, range 41-79 years. The majority of patients, 27 (63%) were men and 16 (37%) were women. Patients were treated with venetoclax in the first and higher line, in combination with obinutuzumab, with rituximab, and in monotherapy. Of these, 16 (37%) patients were after previous treatment with ibrutinib. Treatment indications and response assessment were based on the 2018 international workshop on the Chronic Lymphocytic Leukemia (iwCLL) Criteria. Patients were evaluated after at least 2 months of treatment until disease progression. The effect of treatment was assessed by objective examination of the patient, possibly by imaging examination (USG, CT scan) and evaluation of blood parameters. Adverse effects were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. In case of disease progression, treatment was interrupted. The results of our work confirmed the efficacy and safety of venetoclax in combination with obinutuzumab, and rituximab, even as monotherapy in patients with CLL. The efficacy of the above regimens in our group of patients is comparable to that in clinical studies, even in patients with high-risk genetic features, such as 17p deletion and unmutated IgVH status. Treatment with venetoclax was also effective and well tolerated in patients after previous treatment with ibrutinib. The limitations of our evaluation are the small patient population and the short median follow-up of patients. In line with the conclusions of clinical trials and retrospective analysis from real-life practice, we can say that venetoclax-based treatment regimens are highly effective in patients with CLL in the first and higher line of treatment, with acceptable and well-manageable toxicity. This treatment is also effective in patients after previous treatment with ibrutinib.
EGFR/STAT3 signaling mediates the upregulation of CD47 in HPV-positive cervical cancer by activating p65 and exosome transporter RAB31.
Ke X, Li L, Yan Q … +2 more , Wang X, Liu P
Neoplasma · 2025 Apr · PMID 40353624 · Publisher ↗
In cervical cancer, the regulatory mechanisms of CD47 and its enrichment in exosomes have not been fully elucidated. In this study, we aim to explore the mechanisms of how EGFR/STAT3 signaling regulates CD47 expression i...
In cervical cancer, the regulatory mechanisms of CD47 and its enrichment in exosomes have not been fully elucidated. In this study, we aim to explore the mechanisms of how EGFR/STAT3 signaling regulates CD47 expression in cervical cancer, and whether p65 or RAB31 is involved in this process. RNA interference was used to knock down the fragment of HPV in cervical cancer cells. EGFR and RAB31 phosphorylation were detected by western blot, and exosomal CD47 was determined by ELISA. EGFR or STAT3 was then knocked down and western blot was used to detect the expression or phosphorylation of EGFR, STAT3, p65, CD47, RAB31, and its related proteins. ChIP-qPCR was used to investigate p65 enrichment in the CD47 promoter region. Our results showed that HPV fragment knockdown reduced the phosphorylation of EGFR and RAB31, and exosomal CD47 expression. Knocking down EGFR inhibited phosphorylation of STAT3 and p65, and expression of RAB31-related proteins. Phosphorylated p65 was bound to the P3 and P7 promoter regions of CD47. EGFR/STAT3 signaling upregulated CD47 expression by phosphorylating p65 and enhanced exosomal CD47 by activated RAB31. Thus, a dual regulatory role of EGFR/STAT3 signaling on CD47 expression and secretion involving transcriptional factor p65 and exosome transporter RAB31 was demonstrated.
CCL18 derived from M2-polarized tumor-associated macrophages promotes endometrial cancer progression by activating the TWIST1/HMGA1 axis.
Li H, Li J
Neoplasma · 2025 Apr · PMID 40353623 · Publisher ↗
CCL18, originating from M2-polarized tumor-associated macrophages (M2-TAMs) is recognized for its vital role in endometrial cancer (EC) development. Nonetheless, its precise mechanisms remain largely undefined. The prima...
CCL18, originating from M2-polarized tumor-associated macrophages (M2-TAMs) is recognized for its vital role in endometrial cancer (EC) development. Nonetheless, its precise mechanisms remain largely undefined. The primary objective of this research was to elucidate the underlying mechanism of M2-TAM-isolated CCL18 in EC progression. TWIST1 and HMGA1 expressions were assessed in EC tissues and cells by qRT-PCR or western blotting. M2 macrophages were differentiated from human monocyte THP-1 cells, and characterized via flow cytometry and western blotting. CCL18 levels were evaluated using western blotting and ELISA assay. CCK8, Transwell, and wound healing assays were employed to assess EC cell vitality, invasion, and migration, respectively, while western blotting was utilized to measure related protein markers. The binding relationship between TWIST1 and HMGA1 was validated via ChIP and dual-luciferase reporter assays. TWIST1 and HMGA1 were increased in EC tissues and cells. After being treated with M2-TAM-isolated CCL18, EC cell vitality, migration, and invasion were enhanced. Additionally, CCL18 derived from M2-TAM upregulated TWIST1 levels in EC cells. Further mechanistic analyses unveiled that TWIST could positively regulate HMGA1 in EC cells. Notably, HMGA1 knockdown restrained the malignancy of EC cells, which was reversed by TWIST1 overexpression. M2-TAM-isolated CCL18 facilitated EC progression by activating the TWIST1/HMGA1 axis. These observations might offer new directions for developing targeted curative interventions for EC.
Research progress on the regulation mechanism of DEPTOR expression and its role in tumorigenesis.
Jiang J, Zhao C, Yang M … +2 more , Zhao G, Shu J
Neoplasma · 2025 Apr · PMID 40162510 · Publisher ↗
The mammalian target of rapamycin (mTOR) is a critical sensor and integrator of extracellular stimuli and intracellular signaling pathways, forming structurally and functionally distinct protein complexes (mTORC1, mTORC2...
The mammalian target of rapamycin (mTOR) is a critical sensor and integrator of extracellular stimuli and intracellular signaling pathways, forming structurally and functionally distinct protein complexes (mTORC1, mTORC2, and mTORC3) with various proteins. It serves as a central regulator of vital biological processes like cell proliferation, survival, and autophagy. Numerous studies have linked mTOR pathway activation to tumor progression. DEPTOR, a common negative regulator of mTORC1 and mTORC2, exhibits complex loop regulatory mechanisms beyond simple mTOR pathway modulation. Depending on the cell type or tissue environment, DEPTOR can act as either an oncogene or a tumor suppressor gene. Given its complex role in tumorigenesis, precise regulation of DEPTOR expression across different tumor types is imperative. DEPTOR has emerged as a key focus in research on human malignant tumors. While recent years have seen through investigations into DEPTOR expression regulation in tumors, a systematic literature review is lacking. This review provides a detailed summary of the mechanisms regulating DEPTOR expression, an mTOR inhibitor in tumors, covering DNA induction, transcription, translation, and post-translational modification. Additionally, it explores the potential applications of DEPTOR/mTOR signaling axis-related compounds in tumor therapy.
Inhibition of enzymatic activity of HRD1 results in death of cells derived from glioblastoma multiforme, neuroblastoma, and normal astrocytes.
Guzikova J, Liskova M, Hudak L … +4 more , Brodnanova M, Evinova A, Hatok J, Racay P
Neoplasma · 2025 Apr · PMID 40162509 · Publisher ↗
The aim of the present study was to examine the impact of LS-102, an inhibitor of enzymatic activity of HRD1 that is an essential E3 ubiquitin ligase of endoplasmic reticulum associated degradation (ERAD) on survival of...
The aim of the present study was to examine the impact of LS-102, an inhibitor of enzymatic activity of HRD1 that is an essential E3 ubiquitin ligase of endoplasmic reticulum associated degradation (ERAD) on survival of the human cell lines derived from glioblastoma multiforme (GBM), neuroblastoma, and astrocytes. We have also examined molecular responses to HRD1 inhibition with a focus on proteins playing an essential role in unfolded protein response (UPR) and ERAD. In addition, activation of IRE1α documented by XBP1 splicing was investigated. Finally, we have examined the impact of LS-102 on p53 expression in GBM cells. Inhibition of HRD1 enzymatic activity results in cell death of all tested cells. With respect to GBM cells, U87 cells are more sensitive to LS-102 as T98G cells. Cells of cell lines derived from normal astrocytes K1884 exhibit the highest sensitivity to LS-102 among all cell types used in the study while NHA cells are the most resistant. Sensitivity of neuroblastoma SH-SY5Y cells to LS-102 is comparable to the sensitivity of U87 cells. In GBM cells, inhibition of HRD1 results in induction of the expression of proteins playing an essential role in UPR and ERAD (HRD1, SEL1L, and GRP78). XBP1 splicing induced by HRD1 inhibition was documented in T98G and K1884 cells. We did not observe induction of p53 expression in U87 cells. Since LS-102 induces cell death of normal astrocytes, it is not a candidate for the testing of its potential use as an antitumor treatment of GBM.
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