International journal of oncology最新文献

Non‑small cell lung cancer (NSCLC) is a malignant tumor of significant clinical relevance. Curcumin has been investigated for its potential anticancer properties, as it has been reported to act through multiple cancer‑related targets and pathways. The present study aimed to explore the effects of curcumin in NSCLC using both in vitro and in vivo models. NSCLC cell lines (specifically, A549 and NCI‑H1299 cells), and a mouse tumor model established through the subcutaneous injection of A549 cells, were utilized to evaluate the effects of curcumin intervention. The effects of treatment with curcumin on NOD‑like receptor pyrin domain‑containing 3 (NLRP3) ubiquitination, cell pyroptosis and pyroptosis‑associated factors were also evaluated. In addition, Smad ubiquitination regulatory factor 2 (Smurf2) was analyzed via a series of knockdown and overexpression experiments, both in vitro and in vivo, aimed at investigating its association with curcumin and NLRP3. The results obtained from these experiments showed that curcumin inhibited NSCLC cell growth, promoted pyroptosis and reduced the level of NLRP3 ubiquitination. NLRP3 knockdown reversed the curcumin‑induced increase in pyroptosis‑associated factors both in vitro and in vivo. Additionally, Smurf2 interacted with NLRP3 and alterations in Smurf2 expression levels influenced NLRP3 ubiquitination and cell pyroptosis. Moreover, molecular docking analysis demonstrated that curcumin could bind directly to Smurf2, which subsequently led to an inhibition of Smurf2 activity. Knockdown of Smurf2 enhanced curcumin's ability to stabilize NLRP3 and to promote pyroptosis, whereas Smurf2 overexpression negated these effects. In the in vivo animal model, curcumin treatment led to reduced tumor volumes and weights, in addition to a decreased expression level of Ki67 and increased expression levels of NLRP3 and pyroptosis‑associated factors. Similarly, these effects were enhanced or reversed by Smurf2 knockdown or overexpression, respectively. In conclusion, the findings of the present study showed that curcumin inhibited Smurf2 activity, thereby promoting NLRP3‑dependent pyroptosis in NSCLC cells. In addition, these findings have provided mechanistic insights into the role of curcumin in NSCLC, opening an avenue for its potential therapeutic application.

Bladder cancer (BCa) is a prevalent malignant neoplasm of the urinary tract with high incidence rate, frequent recurrence and rapid disease progression. Conventional approaches for diagnosing, prognosticating and monitoring BCa often rely on invasive procedures such as cystoscopy and tissue biopsy, which are associated with high costs and low patient compliance for follow‑up. Liquid biopsies have advantages, such as being non‑invasive, real‑time, and reproducible, in obtaining diverse biomarkers derived from cellular, molecular, proteomic and genetic signatures in urine or plasma samples. Although plasma‑based biomarkers have been clinically validated, urine provides greater specificity for directly assessing biological materials from urological sources. The present review summarizes advancements and current limitations in urinary protein, genetic and epigenetic biomarkers for disease progression and treatment response of BC, compares performance and application scenarios of urine and blood biomarkers and explores how urinary biomarkers may serve as an alternative or complementary tool to traditional diagnostic methods. The integration of urine‑based or plasma‑based biomarkers into existing diagnostic workflows offers promising avenues for improving accuracy and efficiency of diagnosis in the management of BCa. Notably, the emergence of synthetic biomarkers and urine metabolites, combined with artificial intelligence or bioinformatic technologies, has promise in the screening of potential targets. Continued research and validation efforts are needed to translate these findings into routine clinical practice, ultimately improving patient outcomes and decreasing the burden of BCa.

Following the publication of the above article, the authors subsequently realized that, during the process of collating the raw data, Fig. 1 [the immunohistochemical (IHC) results for stage IV colorectal cancer (CRC)], Fig. 2A (the control β‑actin blots) and Fig. 5C and D (both the images selected for the clone formation assays, and the histograms showing the quantification of the data) were inadvertently assembled incorrectly. These errors arose as a consequence of the affected files having been named similarly to those of the correct panels. The revised versions of Figs. 1, 2 and 5, now featuring the correct IHC data for stage IV CRC in Fig. 1, the correct control western blots in Fig. 2 and the correct colony formation assay data (and quantification thereof) in Fig. 5, are shown on the next three pages. Note that the correction of these figures does not affect the key findings of the study (either the existing published results or the conclusions reached from the results). The authors thank the Editor of International Journal of Oncology for granting them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 56: 1442‑1454, 2020; DOI: 10.3892/ijo.2020.5027].

Malignant mesothelioma (MM) is a rare but aggressive cancer linked to asbestos exposure and characterized by advanced‑stage disease at presentation. Despite advances in treatment, prognosis remains abysmal, highlighting the imperative for the development of novel biomarkers and treatment approaches. Telomere biology plays a pivotal role in the tumorigenic process and has emerged as a key area in oncology research. Short telomeres have been associated with genomic instability, and substantially shorter telomere length (TL) has been identified in MM, showcasing the potential of TL in risk assessment, early detection, and disease progression monitoring. MM predominantly maintains TL through telomerase activity (TA), which in research has been identified in >90% of MM cases, underscoring the potential of TA as a biomarker in MM. Telomerase reverse transcriptase (TERT) polymorphisms may serve as valuable biomarkers, with research identifying associations between single nucleotide polymorphisms (SNPs) and the risk and prognosis of MM. Additionally, TERT promoter mutations have been associated with poor prognosis and advanced‑stage disease, with the non‑canonical functions of TERT hypothesized to contribute to the development of MM. TERT promoter mutations occur in ~12% of MM cases; C228T, C250T and A161C are the most common, while the distribution and frequency differ depending on histological subtype. Research reveals the promise of the various approaches therapeutically targeting telomerase, with favorable results in pre‑clinical models and inconclusive findings in clinical trials. The present review examines the role of telomere biology in MM and its implications in diagnosis, prognosis, and therapy.

Solute carrier family 25 member 1 (SLC25A1) affects lipid metabolism and energy regulation in multiple types of tumor cell, affecting their proliferation and survival. To the best of our knowledge, however, the impact of SLC25A1 on the proliferation and survival of esophageal squamous cell carcinoma (ESCC) cells has yet to be explored. Here, SLC25A1 expression was detected in ESCC tissues and cell lines. SLC25A1 was silenced or blocked by lentivirus transfection or 2‑[(4‑chloro‑3‑nitrophenyl)sulfonylamino]benzoic acid in ESCC cells. To evaluate the impact of SLC25A1 on in vivo and in vitro proliferation, invasion and migration of ESCC cells, Cell Counting‑Kit, wound healing, colony formation, Transwell, EdU, flow cytometry, tumor xenograft in nude mice, lipid metabolism and energy metabolism detection assays were performed. Reverse transcription‑quantitative PCR and western blot analysis were performed to determine expression of downstream molecules and pathway proteins following the silencing and blockade of SLC25A1. SLC25A1 was significantly overexpressed in ESCC tissue and cell lines. The targeted silencing of SLC25A1 or inhibition of its protein led to a significant decrease in proliferative, invasive and migratory capabilities of ESCC cells, accompanied by increased apoptosis. Additionally, silencing of the SLC25A1 gene significantly inhibited xenograft tumor growth in vivo. The present results indicate that knockdown or blockade of SLC25A1 can significantly impede the malignant biological behavior of ESCC.

Multiple myeloma (MM) is a plasma cell malignancy characterized by clonal proliferation in the bone marrow (BM). Previously, it was reported that G‑protein‑coupled receptor 4 (LGR4) contributed to early hematopoiesis and was associated with poor prognosis in patients with MM. However, the mechanism of cell homing and migration, which is critical for MM progression, remains unclear. In the present study, cell counting, cell cycle and BrdU assays were performed to evaluate cell proliferation. Transwell assay and Xenograft mouse models were performed to evaluate cell migration and homing ability both in vitro and in vivo. I was found that overexpression of LGR4 promotes MM cell adhesion, migration and homing to BM both in vitro, while exacerbating osteolytic bone destruction in vivo. However, the LGR4 knockdown displayed the opposite effect. Further mechanistic studies demonstrated that LGR4 activated the nuclear factor kappa B (NF‑κB) signaling pathway and migration‑related adhesion molecule, thus promoting MM cell homing. Moreover, inhibiting the NF‑κB pathway was found to suppress MM cell homing. These findings identify LGR4 as a critical regulator of myeloma cell migration, homing and tumorigenesis, offering a potential therapeutic strategy for MM treatment.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the western blot assay data shown in Fig. 4G on p. 717 were strikingly similar to data that had appeared in a paper published previously in the journal Molecular Cancer Therapeutics, which had been written by different authors at different research institutes. Moreover, there appeared to be as many as five sets of duplicated protein bands in Fig. 4B and C, including the appearance of apparently the same protein band in different orientations in Fig. 4C in one case, and certain data shown in Fig. 4B and G had apparently been re-used in these figure parts. After having performed an independent assessment of these issues in the Editorial Office, these concerns of the reader were found to have been validated; therefore, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. After having been in contact with the authors, they accepted the decision to retract the paper. The corresponding author, Claudio Festuccia, takes full responsibility for the raised concerns and clarifies that the other co-authors were not directly involved in the preparation of the submitted figures. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 40: 711-720, 2012; DOI: 10.3892/ijo.2011.1270].

Human papillomavirus (HPV)‑positive and -negative head and neck squamous cell carcinoma (HNSCC) are often associated with activation of the phosphatidylinositol 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway due to mutations or amplifications in PI3KCA, loss of PTEN or activation of receptor tyrosine kinases. In HPV‑negative tumors, CDKN2A (encoding p16 protein) inactivation or CCND1 (encoding Cyclin D1 protein) amplification frequently results in sustained cyclin‑dependent kinase (CDK) 4/6 activation. The present study aimed to investigate the efficacy of the CDK4/6 inhibitors (CDKi) palbociclib and ribociclib, and the PI3K/Akt/mTOR pathway inhibitors (PI3Ki) gedatolisib, buparlisib and alpelisib, in suppressing cell viability of HPV‑positive and ‑negative HNSCC cell lines. Inhibitor efficacy was assessed in vitro using MTT assay and western blotting analysis. Cell cycle analysis was performed using flow cytometry and apoptosis was assessed using annexin V staining. Metabolic changes in terms of glycolysis and oxidative metabolism were measured by Seahorse XF96 extracellular Flux analysis. The results of the present study showed that both HPV‑positive and ‑negative HNSCC cell lines were sensitive to PI3Ki. In general, PI3Ki decreased PI3K/Akt/mTOR pathway activity, resulting in apoptosis, and decreased oxidative and glycolytic metabolism. The CDKi were particularly effective in blocking HPV‑negative cell line viability, showing decreased retinoblastoma expression and G1‑phase cell cycle arrest, whereas apoptosis was not induced. Thus, PI3Ki and CDKi efficiently inhibited their respective pathways and HNSCC cell viability in vitro, with the latter occurring only in HPV‑negative cell lines. Whereas PI3Ki induced apoptosis and attenuated cellular metabolism, CDKi led to cell cycle arrest. Further research should be performed to elucidate whether (a combination of) these inhibitors may be effective therapeutic agents for patients with HNSCC.

Angiopoietin‑like 4 (ANGPTL4), a member of the angiopoietin family, plays critical roles in angiogenesis, lipid metabolism and inflammation. It has been demonstrated that ANGPTL4 has significant influence on various diseases. Accumulating evidence has highlighted the impacts of ANGPTL4 on human malignancies. ANGPTL4 is commonly overexpressed in various types of cancer, such as breast, non‑small cell lung, gastric and colorectal cancer. Its upregulation promotes tumor growth, invasion, metastasis and angiogenesis, as well as metabolic reprogramming and resistance to programmed cell death, radiotherapy and chemotherapy. However, ANGPTL4 has also exhibited antitumor effects under certain conditions, indicating its complex roles in tumor biology. The transcriptional regulation of ANGPTL4 is influenced by multiple factors, such as HIF‑1, PPARs, TGF‑β and long non‑coding RNAs. In terms of signaling pathways, STATs, PI3K/AKT and COX-2/PGE2 are important in regulating cellular processes. The present review summarizes the biological functions of ANGPTL4 in tumors and its association with patient prognosis. Furthermore, the key molecular mechanisms and potential reasons for its dual roles in cancer are also discussed. In conclusion, ANGPTL4 is a valuable diagnostic biomarker and a potential therapeutic target for human cancers.

Circular (circ)RNAs participate in colorectal cancer (CRC) occurrence and progression. However, the role of hsa_circ_0004662 (circ_0004662) in CRC remains unknown. Reverse transcription‑quantitative PCR noted high expression of circ_0004662 in CRC compared with normal colorectal epithelial cells. circ_0004662 knockdown inhibited migration of CRC cells in vitro and in vivo; would healing and Transwell assays showed that circ_0004662 overexpression contributed to CRC migration. Nuclear cytoplasmic analysis and fluorescence in situ hybridization revealed localization of circ_0004662 in the nucleus and cytoplasm. CircRNADB databases predicted that circ_0004662 exhibited translational potential and liquid chromatography‑mass spectrometry (LC‑MS) of circ_0004662 pull‑down products suggested that circ_0004662 bound to multiple ribosomal subunits. However, peptide products of 149aa translated by circ_0004662, with a molecular weight of ~17 kDa were not detected. Nevertheless, LC‑MS analysis indicated that circ_0004662 bound multiple proteins. Immunoprecipitation of RNA‑binding proteins revealed that circ_0004662 bound to heterogeneous nuclear ribonucleoprotein M (hnRNPM) and that hnRNPM interference decreased circ_0004662 expression, thereby affecting CRC progression. In summary, circ_0004662 was significantly upregulated in CRC. As a non‑coding RNA, it may promote CRC progression by binding to hnRNPM, which may serve as a potential target for treating CRC.