Neoplasma[JOURNAL]
Sun
200 papers
Elevated expression of HSF1 promotes the progression of colorectal cancer by activating CLDN3 transcription.
Shao Y, Ma T, Ma D … +7 more , Hong L, Lv M, Zhou S, Fang Z, Yu E, Li X, Zhu Y
Neoplasma · 2025 Apr · PMID 40162508 · Publisher ↗
Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with increasing morbidity and mortality. Heat shock transcription factor 1 (HSF1), as an important transcription factor regulating the exp...
Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with increasing morbidity and mortality. Heat shock transcription factor 1 (HSF1), as an important transcription factor regulating the expression of heat shock proteins, has been proven to play a crucial role in the development of various tumors. Yet the potential mechanism and clinical significance of HSF1 in CRC remain unclear and require further exploration. We used TCGA database to understand the clinical significance of HSF1 in CRC. Then, we verified the expression of HSF1 in CRC tissues by immunohistochemistry and analyzed its clinical significance. By constructing stable knockdown and overexpressed of HSF1 in cell lines to investigate the potential mechanisms of HSF1 to regulate CRC cell proliferation, migration, and invasion in vivo and in vitro. Next, differential genes expressed by HSF1 in CRC were analyzed by bioinformatics technology, and their correlation and interaction were verified by PCR, WB, and CHIP experiments. We confirmed that HSF1 is highly expressed in CRC and its upregulation is associated with poor prognosis of malignant events in CRC. Functionally, HSF1 can enhance the proliferation, invasion, and migration of CRC cell lines. In vivo experiments have shown that knockdown of HSF1 can inhibit tumor growth. In terms of molecular mechanism, we found that HSF1 can directly bind to the transcription factor binding site of CLDN3 and activate its transcription. Our research demonstrates the clinical significance and carcinogenic effect of HSF1. The functional mechanisms of HSF1 and its targets may serve as diagnostic and therapeutic targets for CRC.
Efficacy and prognostic factors of PD-1 inhibitors combined with apatinib in advanced diffuse gastric cancer.
Chen B, Zhao H, Hu H … +11 more , Huang J, Liu Y, Lv H, Xu W, Wang J, Nie C, Zhao J, He Y, Wang S, Wang Y, Chen X
Neoplasma · 2025 Apr · PMID 40162507 · Publisher ↗
Refractory diffuse gastric cancer (DGC) is rising in incidence and has a bad prognosis. Individuals who are administered second-line or subsequent therapies frequently exhibit diminished physical fitness, rendering them...
Refractory diffuse gastric cancer (DGC) is rising in incidence and has a bad prognosis. Individuals who are administered second-line or subsequent therapies frequently exhibit diminished physical fitness, rendering them inappropriate for intensive treatment. Despite this, PD-1 inhibitors and anti-angiogenesis drug apatinib have demonstrated efficacy in advanced gastric cancer. This study aimed to evaluate the effectiveness, prognostic factors, and safety of PD-1 inhibitors in combination with apatinib in advanced DGC. The present study is a retrospective analysis of 34 patients with advanced DGC treated with apatinib combined with PD-1 inhibitors in the Affiliated Cancer Hospital of Zhengzhou University from 2019 to 2022. Apatinib 250 mg was administered to patients once a day. The median progression-free survival (mPFS) and the median overall survival (mOS) were estimated using Kaplan-Meier curves, whereas objective response rate (ORR), disease control rate (DCR), prognostic variables, and adverse events were among the other outcomes. Data from 34 patients were collected, and the ORR was 5.9% (2 out of 34), while the DCR was 55.9% (19 out of 34). The mPFS was 2.5 months (95% CI: 1.9-3.0), while the mOS was 6.8 months (95% CI: 3.7-9.9). Log-rank univariate analysis indicated that the mOS of patients with carcinoembryonic antigen (CEA) levels <4.7 ng/ml (11.3 months, 95% CI: 7.1-15.5) was significantly different from those with levels ≥4.7 ng/ml (2.7 months, 95% CI: 0.0-6.1) (p=0.008). A notable disparity in mOS and mPFS was observed between patients with CA125 <35 U/ml (7.7 months, 95% CI: 3.6-11.9) and those with CA125 ≥35 U/ml (2.5 months, 95% CI: 1.9-3.0) (p=0.003), as well as between patients with lactate dehydrogenase (LDH) <245 U/l (11.3 months, 95% CI: 7.2-15.5) and those with LDH ≥245 U/l (2.2 months, 95% CI: 1.5-2.9) (p=0.007), and between patients with PLTs <350×109/l (7.5 months, 95% CI: 6.4-8.7) compared to those with PLTs ≥350×109/l (1.7 months, 95% CI: 0.0-3.9) (p=0.001). Multivariate Cox regression analysis indicated that CA125, LDH, and PLT levels were independent prognostic variables. The occurrence of grade 3 or 4 treatment-related adverse events was 17.6% (6/34). The study suggests that the integration of PD-1 inhibitors and apatinib in second-line and subsequent therapies demonstrated promising efficacy and acceptable safety in advanced DGC patients. The concentrations of CA125, LDH, and PLTs may serve as prognostic indicators for DGC.
20(S)-ginsenoside Rg3 induced the necroptosis of prostate cancer cells via ROS overproduction.
Peng Y, Guo Y, Zhao S … +7 more , Yan H, Hao Z, Zheng F, Zhang Z, Miao L, Sun LK, Cuendet M
Neoplasma · 2025 Apr · PMID 40162506 · Publisher ↗
Necroptosis is a programmed form of necrosis, and compounds inducing necroptosis may contribute to cancer treatment. 20(S)-ginsenoside Rg3 is a natural compound extracted from ginseng, which exhibited a broad-spectrum of...
Necroptosis is a programmed form of necrosis, and compounds inducing necroptosis may contribute to cancer treatment. 20(S)-ginsenoside Rg3 is a natural compound extracted from ginseng, which exhibited a broad-spectrum of antitumor activity. In the present study, the potential role of 20(S)-ginsenoside Rg3 in inducing necroptosis in prostate cancer cells was evaluated. 20(S)-ginsenoside Rg3 inhibited the proliferation of prostate cancer cells and upregulated the expression of necroptotic proteins such as receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, and their downstream mixed lineage kinase domain-like protein (MLKL). Pretreatment with the selective RIPK1 inhibitor necrostatin-1 (Nec-1) partially reversed the inhibitory effect of 20(S)-ginsenoside Rg3 on prostate cancer cell proliferation. 20(S)-ginsenoside Rg3 led to the accumulation of reactive oxygen species (ROS) and the regulation of autophagy in cancer cells. Scavenging ROS with N-acetyl-L-cysteine (NAC) antagonized the regulatory effects of 20(S)-ginsenoside Rg3 on cell autophagy and necroptotic proteins expression. Moreover, 20(S)-ginsenoside Rg3 exhibited an antitumor effect in a prostate cancer xenograft mouse model in which it upregulated the expression of RIPK1, RIPK3, MLKL and led to a decrease in tumor weight, as well as an increase in necrotic areas in tumor tissue. In conclusion, our study showed that 20(S)-ginsenoside Rg3 might induce necroptosis in prostate cancer in vitro and in vivo via the ROS/autophagy signaling pathway.
Triptonide inhibits the progression of oral squamous cell carcinoma by suppressing the TRIP13/c-Myc axis.
Zhang H, Wei Z, Han S … +1 more , Zhao S
Neoplasma · 2025 Apr · PMID 40162505 · Publisher ↗
Triptonide, an active ingredient of Tripterygium wilfordii Hook. F., has been found to have anticancer effects on various cancers; however, its effect on oral squamous cell carcinoma (OSCC) has not yet been studied. This...
Triptonide, an active ingredient of Tripterygium wilfordii Hook. F., has been found to have anticancer effects on various cancers; however, its effect on oral squamous cell carcinoma (OSCC) has not yet been studied. This study aims to reveal the effect and mechanism of triptonide on OSCC. The inhibitory effect of triptonide on OSCC progression was ascertained by CCK-8 assay, EdU incorporation assay, wound healing assay, Transwell assay, and xenograft tumor model, while western blotting, qRT-PCR, and immunohistochemistry revealed that triptonide could inhibit c-Myc expression in OSCC. RNA-seq was conducted to explore the mechanism by which triptonide inhibited the progression of OSCC, and thyroid hormone receptor interactor 13 (TRIP13) was identified as a key differentially expressed gene. TRIP13-knockdown OSCC cells constructed with siRNA showed weaker progression ability in CCK-8 assay, EdU incorporation assay, wound healing assay, and Transwell assay. Finally, TRIP13-overexpressing OSCC cells constructed through plasmid were used in rescue experiments, which demonstrated that TRIP13 was located upstream of c-Myc and the overexpression of TRIP13 could partially restore the decreased c-Myc expression caused by triptonide treatment. Collectively, this study demonstrated that triptonide might reduce the expression of c-Myc by suppressing TRIP13 expression, thereby inhibiting the progression of OSCC. These findings have revealed a partial mechanism by which triptonide acts on OSCC and suggested its potential application value in OSCC treatment.
Nuclear factor I-C aggravates acute myelogenous leukemia by inhibiting SRY-box transcription factor 1 to activate autophagy.
Luo C, Luo Z, Li J … +4 more , Wen F, Cao Y, Liu Q, Long X
Neoplasma · 2025 Apr · PMID 40162504 · Publisher ↗
Despite advances in chemoradiotherapy and hematopoietic stem cell transplantation, the treatment of acute myeloid leukemia (AML) remains challenging due to significant side effects and poor prognosis. This study aimed to...
Despite advances in chemoradiotherapy and hematopoietic stem cell transplantation, the treatment of acute myeloid leukemia (AML) remains challenging due to significant side effects and poor prognosis. This study aimed to investigate the role of nuclear factor I-C (NFIC) in AML progression by evaluating whether NFIC exacerbates AML through the inhibition of SRY-box transcription factor 1 (SOX1) and activation of autophagy, thereby providing potential insights for clinical treatment. NFIC and SOX1 expression levels in AML and normal samples were analyzed using bioinformatics, ELISA, RT-qPCR, and western blotting, and the interaction between NFIC and SOX1 was assessed through RNA pull-down and RNA-binding protein immunoprecipitation assays. Moreover, CCK-8 assay, FITC/PI apoptosis detection, immunofluorescence staining, RT-qPCR, and western blotting were conducted to assess cell viability, apoptosis, and the expression of NFIC, SOX1, Bax, Bcl-2, LC3-I, LC3-II, p62, and Beclin-1 following gene transfection. NFIC expression was significantly upregulated in AML samples while SOX1 expression was downregulated compared to normal controls. High NFIC levels were associated with poor prognosis in AML patients, and it was found to regulate SOX1 expression in KG-1 and NB4 cells negatively. Silencing NFIC or overexpressing SOX1 resulted in reduced cell viability and autophagy, and increased apoptosis in KG-1 and NB4 cells. Importantly, NFIC knockdown did not affect apoptosis in bone marrow mononuclear cells. The adverse effects of NFIC overexpression were reversed by SOX1 overexpression, highlighting the interplay between these factors in AML. This study demonstrates that NFIC promotes AML progression by activating autophagy and suppressing apoptosis in KG-1 and NB4 cells by inhibiting SOX1, providing a potential basis for therapeutic strategies targeting NFIC and SOX1 in AML.
circ_0075829 regulates ferroptosis and immune escape in colon cancer cells through the miR-330-5p/TCF4 axis.
Fan H, Ding Y, Xiao Z … +2 more , Li S, Zheng Y
Neoplasma · 2024 Dec · PMID 39832206 · Publisher ↗
Many lines of evidence suggest that circular RNAs (circRNAs) are closely associated with the occurrence and progression of colon cancer. The objective of this study was to investigate the regulatory effects and mechanism...
Many lines of evidence suggest that circular RNAs (circRNAs) are closely associated with the occurrence and progression of colon cancer. The objective of this study was to investigate the regulatory effects and mechanisms of circ_0075829 on ferroptosis and immune escape in colon cancer. We utilized colon cancer cell lines and a xenograft mouse model to analyze the function of circ_0075829 in vitro and in vivo. The gene expression level was assessed by qRT-PCR and western blotting. Cell proliferation was evaluated using the CCK-8 assay. The targeting relationships between circ_0075829, miR-330-5p, and TCF4 were analyzed through a dual-luciferase reporter experiment and RNA pull-down experiment. Cytokine levels were measured using the ELISA assay. Fe2+, MDA, and SOD levels were tested using appropriate kits, and the ROS level was detected by immunofluorescence. Knockdown of circ_0075829 resulted in increased levels of Fe2+, ROS, and MDA and decreased levels of GPX4 and xCT proteins in cells. Furthermore, silencing of circ_0075829 increased the cell proliferation rates of CD8+T cells co-cultured with colon cells. Moreover, it also enhanced IFN-γ, IL-2, and TNF-α concentration in the supernatants of the co-culturing system and reduced PD-L1 protein expression levels. Subsequently, silencing of circ_0075829 induced ferroptosis and inhibited immune escape in vivo. Meaningfully, we certified that circ_0075829 functions as a sponge for miR-330-5p, leading to the upregulation of TCF4 expression. TCF4 was identified as a downstream target of miR-330-5p. Additionally, co-transfection with anti-miR-330-5p or TCF4 overexpression plasmid reversed the effects observed following the knockout of circ_0075829. Collectively, our research indicates that the circ_0075829 plays a significant role in regulating ferroptosis and immune escape in colon cancer by sponging miR-330-5p to modulate TCF4 expression.
hsa_circ_0021727 facilitates esophageal squamous cell carcinoma progression by stabilizing GBX2 mRNA through interacting with EIF4A3.
Lin J, Zhu Q, Zeng F
Neoplasma · 2024 Dec · PMID 39832205 · Publisher ↗
Esophageal squamous cell carcinoma (ESCC) has high mortality. The role and regulatory mechanism of hsa_circ_0021727 (circ_0021727) in ESCC remain largely unknown. This study focused on the undiscovered impact of circ_002...
Esophageal squamous cell carcinoma (ESCC) has high mortality. The role and regulatory mechanism of hsa_circ_0021727 (circ_0021727) in ESCC remain largely unknown. This study focused on the undiscovered impact of circ_0021727 on cell cycle progression, apoptosis, and angiogenesis of ESCC. We found that circ_0021727 levels were significantly upregulated in ESCC cells. TUNEL, flow cytometry, and tubule formation assay indicated that knockdown of circ_0021727 in ESCC induced cell arrest at the G0/G1 phase, promoted apoptosis, and inhibited angiogenesis, whereas overexpression of circ_0021727 produced the opposite effect. Gastrulation brain homeobox 2 (GBX2) GBX2 was a downstream target gene of circ_0021727, and overexpression of GBX2 reversed the effect of circ_0021727 knockdown in ESCC progression. The results of the RIP and RNA pull-down showed that circ_0021727 and GBX2 mRNA bound with eukaryotic translation initiation factor 4A3 (EIF4A3). Overexpression of circ_0021727 promoted GBX2 mRNA stability by binding with EIF4A3. In a tumor xenograft model, the knockdown of circ_0021727 inhibited tumor growth, which was reversed by further overexpression of GBX2. In conclusion, circ_0021727 increased GBX2 mRNA stability by recruiting EIF4A3, which promoted cell cycle progression and angiogenesis in ESCC.
Negative prognostic significance of primary cilia and cytoplasmic β-catenin expression in non-small cell lung cancer.
Rosova B, Filipova A, Hadzi Nikolov D … +9 more , Drösslerova M, Matej R, Rozsypalova A, Richter I, Melichar B, Mahel R, Stepanova R, Lohynska R, Dvorak J
Neoplasma · 2024 Dec · PMID 39832204 · Publisher ↗
The objective of this study was to investigate the prognostic significance of the frequency of primary cilia (PC) and β-catenin expression in 218 patients (pts) with non-small cell lung cancer (NSCLC), including 125 pts...
The objective of this study was to investigate the prognostic significance of the frequency of primary cilia (PC) and β-catenin expression in 218 patients (pts) with non-small cell lung cancer (NSCLC), including 125 pts with adenocarcinoma and 93 pts with squamous cell carcinoma. In the whole group of 218 pts with NSCLC, overall survival (OS) was significantly inferior among pts with present PC than without PC (p=0.024) and with higher cytoplasmic β-catenin expression (25-75%) than with lower cytoplasmic β-catenin expression (<25%) (p=0.008). In the univariate Cox proportional hazard model, the hazard ratio was 1.653 in pts with present PC (p=0.026) and 1.851 in pts with higher cytoplasmic β-catenin (25-75%) (p=0.009). Multivariate testing of the whole group of 218 pts with NSCLC showed that the presence of PC was associated with a worse prognosis (p=0.018). In the subgroup of 125 pts with adenocarcinoma, OS was significantly improved in pts with higher membranous β-catenin expression (≥50%) than in pts with lower expression (<50%) (p=0.0300) and OS was significantly inferior in pts with higher cytoplasmic β-catenin expression (25-75%) than in pts with lower expression (<25%) (p=0.0004). Multivariate testing of the subgroup of pts with adenocarcinoma showed that cytoplasmic β-catenin (p<0.001) and pleural invasion (p=0.017) were associated with worse prognosis. The present results indicate a negative prognostic significance of PC and cytoplasmic β-catenin expression in NSCLC and a negative prognostic significance of cytoplasmic β-catenin expression in adenocarcinoma.
Methylation status of selected genes in non-small cell lung carcinoma - current knowledge and future perspectives.
Put A, Smesny Trtkova K, Skarda J
Neoplasma · 2024 Dec · PMID 39832203 · Publisher ↗
DNA methylation is recognized as an early event in cancer initiation and progression. This review aimed to compare the methylation status of promoter regions in selected genes across different histological subtypes of no...
DNA methylation is recognized as an early event in cancer initiation and progression. This review aimed to compare the methylation status of promoter regions in selected genes across different histological subtypes of non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and the rare but highly aggressive large-cell neuroendocrine carcinoma (LCNEC). A comprehensive literature search was conducted in the PubMed database until August 17, 2024, using standardized keywords to identify reports on promoter methylation in NSCLC. Seventy-five studies were reviewed, focusing on the promoter methylation of key genes, such as APC, BRCA1, CDH1, CDH13, DAPK1, DLEC1, FHIT, GSTP1, hMLH1, MGMT, CDKN2A, RARβ, RASSF1, RUNX3, and TIMP3. These studies explored diagnostic, prognostic, epidemiological, and therapeutic aspects across NSCLC subtypes. Additionally, mutational profiles of TP53, RB1, KEAP1, and STK11 and expression patterns of ASCL1, DLL3, and NOTCH were analyzed. The findings suggest that LCNEC may serve as a biological bridge between non-small cell and small-cell lung carcinoma. Our analysis highlights that the methylation status of selected genes could enhance diagnosis, prognosis, and personalized treatment strategies in patients with NSCLC, particularly those with LCNEC.
MTHFD2 promotes breast cancer cell proliferation through IFRD1 RNA m6A methylation-mediated HDAC3/p53/mTOR pathway.
Zhang Q, Mao J, Xie L … +4 more , Lu Y, Li X, Yu X, Li L
Neoplasma · 2024 Dec · PMID 39832202 · Publisher ↗
MTHFD2 is highly overexpressed in breast cancer tissues, indicating that it might be used as a target in breast cancer treatment. This study aims to determine the role of MTHFD2 in breast cancer cell proliferation and th...
MTHFD2 is highly overexpressed in breast cancer tissues, indicating that it might be used as a target in breast cancer treatment. This study aims to determine the role of MTHFD2 in breast cancer cell proliferation and the molecular pathways involved. In order to investigate MTHFD2 gene expression and its downstream pathways in breast cancer, we started our inquiry with a bioinformatics analysis. We then engineered breast cancer cell lines with either silenced or overexpressed MTHFD2 to study its effects on the cell cycle, proliferation, and the m6A methylation status of the gene IFRD1, predicted as a downstream target. Overexpression of MTHFD2 enhanced cellular proliferation, increased the proportion of EdU-positive cells, and accelerated progression into the S+G2/M phase. In contrast, MTHFD2 knockdown led to opposite effects. MTHFD2 and IFRD1 expression levels showed a strong positive association. Increased MTHFD2 activity boosted HDAC3 and mTOR phosphorylation, activating p70 S6K and 4EBP1-key regulators of cell proliferation. Moreover, overexpression of MTHFD2 was associated with reduced p53 acetylation and total protein levels. Silencing MTHFD2 decreased m6A methylation of IFRD1 RNA, whereas its overexpression increased methylation. Notably, IFRD1 siRNA transfection reversed the proliferative effects induced by MTHFD2 overexpression. Furthermore, MTHFD2 knockdown enhanced the sensitivity of breast cancer cells to several chemotherapeutic agents. In conclusion, MTHFD2 influences breast cancer cell proliferation by modulating the m6A methylation of IFRD1 RNA, which regulates the HDAC3/p53/mTOR pathway. These findings suggest that MTHFD2 inhibitors may synergistically enhance the efficacy of existing chemotherapies.
IFIH1 promotes apoptosis through the TBK1/IRF3 pathway in triple-negative breast cancer.
Shi C, Wang X, Li J … +5 more , Wu S, Liu Z, Ren X, Zhang X, Liu Y
Neoplasma · 2024 Dec · PMID 39832201 · Publisher ↗
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast malignancy. Although some patients benefit from immune checkpoint therapy, current treatment methods rely mainly on chemotherapy. It is impera...
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast malignancy. Although some patients benefit from immune checkpoint therapy, current treatment methods rely mainly on chemotherapy. It is imperative to develop predictors of efficacy and identify individuals who will be sensitive to particular treatment regimens. This study analyzed peripheral interferons and immune cell subsets in TNBC patients receiving pre-operative neoadjuvant therapy. The effects of interferon-induced helicase 1 (IFIH1) on the biological characteristics of apoptosis and PD-L1 expression of cancer cells and its potential mechanism were investigated using bioinformatics analysis, clinical specimens, and in vitro study. We found that serum interferon-γ and interferon-α2 levels were significantly higher in TNBC patients with pathologic complete response (pCR). The expression of IFIH1 is markedly upregulated in various tumors, including breast cancer. Immunohistochemical results revealed that IFIH1 was specifically located in the cytoplasm of cancer cells. Gene set enrichment analysis showed that genes co-expressed with IFIH1 were involved in tumor immune-related pathways and apoptosis. Knockdown of IFIH1 in MDA-MB-231 and BT-549 cells resulted in significantly increased cell proliferation and colony formation. Regarding apoptosis-related pathway proteins, there was a significant decrease in levels of phosphorylated TANK-binding kinase 1 (TBK1) and phosphorylated interferon regulatory factor 3 (IRF3). In addition, the expression of PD-L1 was significantly downregulated. Furthermore, we demonstrated the existence of binding sites between IRF3 and PD-L1 promotors. Our data indicate that cancer cell IFIH1 promotes apoptosis and PD-L1 expression, suggesting its potential as a predictive marker of efficacy and therapeutic target in TNBC.
Disruption of lipid raft reverses drug resistance in colorectal cancer cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B pathway and P-glycoprotein.
Chen J, Zheng W, Li Q … +3 more , Xu R, Bai T, Pan C
Neoplasma · 2024 Dec · PMID 39832200 · Publisher ↗
Regarding flotillin knockdown, drug resistance is reversed in colorectal cancer (CRC) cell lines; this is associated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, as our previous experimental re...
Regarding flotillin knockdown, drug resistance is reversed in colorectal cancer (CRC) cell lines; this is associated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, as our previous experimental results indicated. However, the exact mechanism underlying this pathway remains unclear. PI3K inhibitor and activator were added separately to clarify the role of the PI3K pathway in reversing drug resistance. The results showed decreased resistance after inhibiting PI3K activity. Furthermore, the reduced resistance due to flotillin knockdown was restored after adding the PI3K activator. Additional results showed no changes in PI3K molecules. However, p-AKT expression was downregulated. Further results suggested that the phosphatidylinositol (3,4,5)-trisphosphate/phosphatidylinositol 4,5-bisphosphate (PIP3/PIP2) ratio was downregulated, whereas the phosphatase and tensin homolog (PTEN) expression was upregulated. In addition, we also found that P-gp activity inhibition resulted in increased adriamycin accumulation and reversal of resistance, and flotillin knockdown was accompanied by a downregulation of P-gp expression in CRC cells. In conclusion, our study demonstrated that flotillin knockdown could reverse drug resistance in CRC cells by downregulating the PTEN/PI3K/AKT pathway and P-gp.
Clinical features, treatment modalities, and survival rates of pediatric central nervous system tumors: A retrospective analysis from a single center (2000-2020).
Bubláková E, Makohusová M, Ballová A … +10 more , Husáková K, Hederová S, Mocná A, Chrenko R, Trnovec S, Jakešová S, Durdík M, Rýchly B, Hrašková A, Kolenová A
Neoplasma · 2024 Dec · PMID 39832199 · Publisher ↗
Pediatric central nervous system (CNS) tumors represent 20-25% of childhood malignancies, with 35-40 new cases annually in Slovakia. Despite treatment advances, high mortality and poor quality of life in a lot of cases p...
Pediatric central nervous system (CNS) tumors represent 20-25% of childhood malignancies, with 35-40 new cases annually in Slovakia. Despite treatment advances, high mortality and poor quality of life in a lot of cases persist. This study assesses the clinical features, treatment modalities, and survival rates of pediatric CNS tumor patients in the single largest center in Slovakia. A retrospective analysis was conducted on pediatric CNS tumors from January 1, 2000, to December 31, 2020, at the Department of Pediatric Oncology and Hematology at the National Institute of Children's Diseases in Bratislava, Slovakia. Among 397 patients (242 males, 155 females), the most common histological types were astrocytomas (42.8%), followed by embryonal tumors (18.4%), brain stem tumors (10.3%), and ependymal tumors (8.1%). Tumor locations were supratentorial (48.1%), infratentorial (46.9%), and spinal (4.3%). Surgical interventions included radical excision (30.2%), subtotal/partial excision (41.8%), and biopsy (9.3%). Treatment modalities varied, with 31.2% receiving combined surgery, chemotherapy, and radiotherapy; 27.5% surgery alone; 9.6% surgery with radiotherapy; 7.8% chemotherapy only; and 6.3% having no treatment. By 2020, 74.3% of patients were alive, with a 25.7% mortality rate. This study outlines the characteristics of pediatric CNS tumors in Bratislava, highlighting the need for multidisciplinary national and international collaboration to advance diagnosis and treatment. Our data align with global findings from other centers.
Correction: Efficacy and safety analysis of anlotinib in combination with immune checkpoint inhibitors for second-line and subsequent extensive-stage small-cell lung cancer.
Ying X, Shi Z, Shao R … +2 more , You G, Song Z
Neoplasma · 2024 Oct · PMID 39556434 · Publisher ↗
Due to the delayed delivery of the request for a correction and the requirement from the Office of Zhejiang Chinese Medical University to standardize the institution's English translation, the editorial department of NEO...
Due to the delayed delivery of the request for a correction and the requirement from the Office of Zhejiang Chinese Medical University to standardize the institution's English translation, the editorial department of NEOPLASMA has issued a correction in response to the author's signed request: The affiliation of the first author has been changed from "Graduate School of Zhejiang University of Traditional Chinese Medicine" to "Graduate School, Zhejiang Chinese Medical University."
Exploring the role of eIF3m in prostate cancer: regulation of c-Myc signaling pathway and therapeutic implications.
Guo D, Ma C, Gu J … +8 more , Zhai X, Chen X, Ju G, Chu C, Zhan X, Wang T, Tan M, Xu D
Neoplasma · 2024 Oct · PMID 39556433 · Publisher ↗
Prostate cancer (PCa) is the most frequently diagnosed malignant tumor in males, and there are currently few effective therapeutic targets following hormone therapy resistance. Subunits of eukaryotic initiation factor 3...
Prostate cancer (PCa) is the most frequently diagnosed malignant tumor in males, and there are currently few effective therapeutic targets following hormone therapy resistance. Subunits of eukaryotic initiation factor 3 (eIF3) have been implicated in the progression of various cancers. This study aims to investigate the biological functions of the eIF3m subunit in PCa and assess its potential as a novel therapeutic target for treatment. We utilized open-access datasets and patient tissues to analyze the expression and prognostic value of eIF3m in PCa. To explore the role of eIF3m in PCa growth, we established eIF3m knockdown models in PC3 and 22Rv1 cells for both in vitro and in vivo studies. Gene set enrichment analysis (GSEA) was utilized to identify signaling pathways regulated by eIF3m in PCa. Additionally, western blotting and immunochemistry were used to confirm the regulation of c-Myc signaling by eIF3m in PCa. Our results indicated that eIF3m expression was elevated in PCa tissues, with higher levels correlating with an increased risk of biochemical recurrence following radical prostatectomy. Both in vitro and in vivo experiments demonstrated that inhibiting eIF3m significantly impeded the growth of PCa cells. GSEA and immunochemistry further revealed that high eIF3m expression contributed to the activation of c-Myc signaling in PCa patients. Notably, the downregulation of eIF3m resulted in a significant decrease in the expression of c-Myc mRNA and protein in PCa cells. Overall, our findings suggest that eIF3m inhibition significantly suppressed PCa cell growth and c-Myc signaling, indicating that eIF3m is a promising therapeutic target for PCa patients.
Determination of serum vitamin D in patients with renal, bladder, and prostate cancer by ultra-performance liquid chromatography-tandem mass spectrometry.
Huang Z, Zhang W, Huang K … +1 more , Feng J
Neoplasma · 2024 Oct · PMID 39556432 · Publisher ↗
The purpose of this study is to detect the vitamin D (VitD) levels in patients with renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PC) using ultra-high performance liquid chromatography-tandem mass...
The purpose of this study is to detect the vitamin D (VitD) levels in patients with renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PC) using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology to assess the VitD status in subjects using different methods, to understand the true level of VitD in RCC, BC, and PC patients. A total of 170 subjects were included in this study, and their serum VitD metabolite levels were measured, including 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25-hydroxyvitamin D3 [C3-epi-25(OH)D3, C3-epi], and calculations for 25(OH)D, 25(OH)D2/25(OH)D3, and C3-epi/25(OH)D3 were made. The variations in serum VitD, calcium (Ca), inorganic phosphorus (IP), vitamin D receptor (VDR), and renal function indicators were measured, and their correlations were analyzed. The levels of 25(OH)D, 25(OH)D3, C3-epi, C3-epi /25(OH)D3, and free 25(OH)D [ F25(OH)D] in RCC, BC, and PC patients were significantly lower than that in the healthy control (HC) group (all p<0.05). The ratio of 25(OH)D2/25(OH)D3 was significantly higher in these groups compared to the HC group (all p<0.05). 25(OH)D3 distinguished the HC group from common cancers of the urinary system (including RCC, BC, and PC) in male patients and showed good diagnostic performance. The level of 25(OH)D3 in all three groups was positively correlated with F25(OH)D levels, and in the disease groups, C3-epi levels were positively correlated with both 25(OH)D3 and F25(OH)D levels. This study found that RCC, BC, and PC patients had lower serum levels of 25(OH)D3, C3-epi, and F25(OH)D compared to healthy individuals, with most RCC, BC, and PC patients displaying VitD deficiency.
The impact of c-Met inhibition on molecular features and metastatic potential of melanoma cells.
Demkova L, Matuskova M, Gercakova K … +3 more , Kozovska Z, Smolkova B, Kucerova L
Neoplasma · 2024 Oct · PMID 39556431 · Publisher ↗
The aberrant activation of the hepatocyte growth factor receptor (c-Met) in malignant melanoma is associated with poor prognosis, fostering tumor progression, angiogenesis, and invasiveness. While therapeutic targeting o...
The aberrant activation of the hepatocyte growth factor receptor (c-Met) in malignant melanoma is associated with poor prognosis, fostering tumor progression, angiogenesis, and invasiveness. While therapeutic targeting of this pathway has shown promise in several tumors, our previous findings revealed increased tumorigenicity following tyrosine kinase inhibitor SU11274 treatment. Therefore, we hypothesized that administering c-Met inhibitors may elicit distinct effects in human melanoma cells. In this study, we investigated the influence of three c-Met inhibitors, SU11274, crizotinib, and PHA665752, on molecular characteristics, tumorigenicity, and metastatic behavior in three human melanoma cell lines, M4Beu, EGFP-A375 and its metastatic variant, EGFP-A375/Rel3 (Rel3). Crizotinib and PHA665752 induced upregulation of MET proto-oncogene, receptor tyrosine kinase (MET), alongside cancer stem cell marker Prominin 1 (CD133), pluripotency marker Nanog homeobox (Nanog), and genes encoding angiogenic factors and receptors in Rel3 cells, correlating with supportive effect on tumorigenicity in vivo. The increased tumorigenicity of the Rel3 cells following the SU11274 treatment correlated with the elevated phosphorylation of Akt, p70 S6 and RSK kinases. Our results demonstrate pleiotropic changes induced by small-molecule inhibitors of receptor tyrosine kinases in melanoma cell lines.
Six2 regulates the malignant progression and 5-FU resistance of hepatocellular carcinoma through the PI3K/AKT/mTOR pathway and DNMT1/E-cadherin methylation mechanism.
Li J, Cheng X, Huang D … +1 more , Cui R
Neoplasma · 2024 Oct · PMID 39556430 · Publisher ↗
This study focuses on exploring the role of Six2 in the progression of hepatocellular carcinoma (HCC) and its resistance to the chemotherapy drug 5-fluorouracil (5-FU). Using Hep3B and Huh7 cell lines, we analyzed how Si...
This study focuses on exploring the role of Six2 in the progression of hepatocellular carcinoma (HCC) and its resistance to the chemotherapy drug 5-fluorouracil (5-FU). Using Hep3B and Huh7 cell lines, we analyzed how Six2 affects various cellular functions, including viability, proliferation, apoptosis, and invasion. Our research also delved into Six2's regulatory impact on DNMT1 levels, E-cadherin expression, and the methylation of the E-cadherin promoter, all of which are crucial for 5-FU resistance in HCC cells. Additionally, we examined the effects of Six2 knockdown on the PI3K/AKT/mTOR signaling pathway. Our findings indicate that overexpression of Six2 enhances cell viability and proliferation, encourages invasive behavior, increases methylation at the E-cadherin promoter, and reduces apoptosis. These changes correspond with increased levels of DNMT1 and decreased levels of E-cadherin, culminating in heightened resistance to 5-FU. Conversely, knocking down Six2 increases the sensitivity of HCC cells to 5-FU and reduces activation of the PI3K/AKT/mTOR pathway. These results suggest that Six2 plays a significant role in promoting HCC proliferation, invasion, and chemotherapy resistance, particularly through mechanisms involving DNMT1 and the PI3K/AKT/mTOR pathway, highlighting its potential as a target for HCC treatment.
EIF4A3-induced circle RNA_ 0001860 promotes growth, invasion, and immune evasion of gastric cancer cells through the miR-618/HMGA2 axis.
Zhang X, Li J, Zhang Q
Neoplasma · 2024 Oct · PMID 39556429 · Publisher ↗
Gastric cancer is a globally common type of cancer with a dismal prognosis. Circle RNA_ 0001860 (circ_0001860) is dysregulated in several cancers and involved in cancer development. Its involvement in stomach cancer, how...
Gastric cancer is a globally common type of cancer with a dismal prognosis. Circle RNA_ 0001860 (circ_0001860) is dysregulated in several cancers and involved in cancer development. Its involvement in stomach cancer, however, remains unclear. AGS and HGC-27 cells were transfected with shRNA against circ_0001860 to knock down the circ_0001860 level. The function of circ_0001860 in gastric cancer was analyzed by cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, Transwell, ELISA, dual-luciferase reporter, RIP, RNA pull-down, and western blotting. Nude mice were subcutaneously inoculated with AGS cells with lentivirus-packaged sh-circ_0001860 to determine the role of sh-circ_0001860 in gastric cancer by immunohistochemistry assays. circ_0001860 was upregulated in gastric cancer, indicating a poor prognosis for gastric cancer patients. Knockdown of circ_0001860 reduced gastric cancer cells' viability, the percentage of EdU-positive cells, the numbers of invaded cells, and concentrations of IL-10 and TGF-β while fostering the concentrations of IFN-γ and IL-2. circ_0001860 sponged miR-618 to positively modulate the HMGA2 level in gastric cancer cells. The inhibitory role of sh-circ_0001860 on cell growth, invasion, and immune evasion of gastric cancer was abolished with the miR-618 knockdown or the HMGA2 overexpression. Besides, EIF4A3 positively modulated the circ_0001860 level in gastric cancer cells. In vivo, silencing of circ_0001860 reduced tumor size and weight and the expression of HMGA2 and IL-10 but enhanced the level of miR-618 and IFN-γ. Collectively, circle RNA_ 0001860 was induced by EIF4A3 to enhance proliferation, invasion, and immune evasion of gastric cancer through the miR-618/HMGA2 axis.
The real-world comparison of non-small cell lung cancer survival outcomes depending on immunotherapy treatment and PD-L1 expression level.
Ondrušová M, Suchanský M, Vándor Svidová S … +6 more , Chowaniecová G, Mriňáková B, Sekerešová M, Juskanič D, Ondruš D, Šenitko M
Neoplasma · 2024 Oct · PMID 39556428 · Publisher ↗
The incidence and mortality trends of lung cancer in Slovakia are not favorable. In our single-center, non-interventional retrospective cohort study, we provide comprehensive information about Slovakia's non-small cell l...
The incidence and mortality trends of lung cancer in Slovakia are not favorable. In our single-center, non-interventional retrospective cohort study, we provide comprehensive information about Slovakia's non-small cell lung cancer (NSCLC) patient population. We evaluated how the introduction of immunotherapy agents affected the survival of NSCLC patients and tried to identify whether the PD-L1 expression level was associated with a negative patient survival effect. The demographics, results of histological and immunohistochemical (PD-L1) examinations, and information about treatment (immunotherapy or standard of care (SOC)) were recorded. In males, squamous cell carcinomas occurred more often than adenocarcinomas (54.40% and 45.08%, respectively), in females, adenocarcinomas clearly dominated (71.88% vs. 27.08%, respectively). The overall proportion of adenocarcinomas was 53.98%. NSCLC patients with stage III and IV treated with SOC treatment (n=54) showed significantly worse overall survival than patients with immunotherapy (n=9) (p=0.026). The comparison of immunotherapy-treated (n=7) and SOC-treated (n=32) adenocarcinoma patients stage III and IV showed similar results (p=0.046). The negative effect of PD-L1 expression level on survival of females with NSCLC and females with adenocarcinoma was visible already at the TPS level of 20-25%. In males with NSCLC, the negative effect was visible at a TPS level of 70-90%. Our results confirm the positive impact of immunotherapy in real-world conditions and show different effects of PD-L1 expression level on patients' survival depending on sex and histology. Determination of different PD-L1 expression breaking points in males and females with NSCLC is a solid starting point for more research on this topic.
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