International journal of oncology最新文献

Hepatocellular carcinoma (HCC) continues to rank as a predominant contributor to cancer‑related mortality on a global scale, attributed to its insidious onset and unfavorable prognosis. The ribosomal protein lateral stalk subunit P0 (RPLP0) has recently gathered widespread attention as a crucial factor in the pathological progression of various neoplasms; however, its exact role in HCC remains inadequately defined. Consequently, the present study endeavored to shed light on the function and mechanistic underpinnings of RPLP0 in HCC and assess its clinical significance and potential as a therapeutic target. qPCR and western blot analyses indicated that RPLP0 was markedly upregulated in HCC, with its elevated levels correlating with poorer survival outcomes. Silencing RPLP0 expression suppressed the proliferative, invasive, migratory, and epithelial‑mesenchymal transition (EMT) abilities of HCC cells, while concurrently promoting apoptosis, autophagy, and G₂/M cell cycle arrest, as evidenced by CCK‑8, colony formation, Transwell assays and flow cytometry analysis, respectively. Moreover, the findings revealed that RPLP0 downregulation mediated the suppression of the JAK2/STAT3 pathway through reactive oxygen species (ROS) accumulation, which in turn downregulated c‑Myc expression. Furthermore, chromatin immunoprecipitation and dual luciferase assays demonstrated that c‑Myc directly bound to the promoter sequence of RPLP0, thereby augmenting its transcriptional activity. In summary, the current study highlighted that RPLP0 establishes a feedback circuit with c‑Myc by facilitating JAK2/STAT3 pathway activation through suppressing ROS levels, while c‑Myc reciprocally activates RPLP0, forming a regulatory circuit loop that drives HCC progression. Thus, targeting the c‑Myc/RPLP0/ROS/JAK2/STAT3 axis emerges as a promising therapeutic strategy for the management of HCC.

Biliary tract cancer (BTC) encompasses a group of aggressive malignancies arising from the bile duct epithelium, including gallbladder cancer and cholangiocarcinoma, which are characterized by aggressive progression, frequent metastases and poor prognoses. BTC accounts for ~3% of all digestive system tumors, with a 5‑year overall survival rate of <20%. BTC presents a clinical challenge. Despite multidisciplinary therapeutic approaches incorporating surgery, chemotherapy and radiotherapy, persistent obstacles, including high tumor recurrence rates (>50%) and the development of treatment resistance remains, underscoring the urgent need for novel treatment strategies such as targeted therapies and immunotherapies. Ferroptosis, a distinct mechanism of regulated cell death triggered by lipid peroxidation, serves critical roles in disease occurrence and progression. Increasing evidence supports the potential of ferroptosis as a targeted therapy in malignancies, with emerging implications for personalized BTC treatment. The present review investigated the molecular mechanisms and signaling pathways that govern ferroptosis, the advances in the understanding of ferroptosis during the initiation and progression of BTC, and the translation potential of ferroptosis for precision therapeutics. By integrating current knowledge, the present study aimed to provide theoretical suggestions for future mechanistic investigations and clinical studies of ferroptosis‑based interventions for patients with BTC.

Gastric cancer (GC) has a high incidence, resistance to chemotherapeutic drugs and a bleak prognosis. Helicobacter pylori (H. pylori) can promote GC development through Correa's cascade by impacting various forms of programmed cell death (PCD). As an iron‑dependent form of PCD, ferroptosis has emerged as a major focus in biomedical research. Notably, there have been developments in elucidating the mechanisms underlying ferroptosis dysregulation throughout Correa's cascade. On one hand, targeting ferroptosis may provide a promising direction for the development of drugs for chronic atrophic gastritis (CAG) and intestinal metaplasia (IM). On the other hand, targeting ferroptosis in GC may be a potential option to overcome the challenges in conventional therapies such as resistance to chemotherapy. Consequently, the present review aims to deliver a comprehensive understanding of the mechanisms underlying ferroptosis dysregulation in H. pylori‑associated GC and summarize the latest progress of ferroptosis‑related studies in CAG, IM and GC. The present study identifies key regulators of ferroptosis at distinct pathological stages, thereby providing insight of novel strategies for the management of precancerous lesion‑related diseases and GC.

Gastric cancer (GC) ranks among the most prevalent malignancies worldwide and is associated with high mortality rates. Ephrin‑B2 (EFNB2), a membrane‑bound ligand that interacts with Eph receptor tyrosine kinases, has been implicated in various cancer‑related biological processes; however, its precise role in GC remains poorly understood. By integrating data from multiple public databases with immunohistochemical analyses of tissue microarrays, significant upregulation of EFNB2 expression in GC specimens compared with paired adjacent normal tissue was demonstrated. Elevated EFNB2 levels were associated with the poor overall survival and disease‑free survival in patients with GC. EFNB2 knockdown inhibited cellular proliferation and viability, increased apoptosis, and induced cell cycle arrest at the G₀/G₁ phase in GC cells. By contrast, EFNB2 overexpression resulted in the opposite oncogenic effects. Mechanistically, rescue experiments identified the Wnt/β‑catenin signaling cascade as the primary molecular pathway mediating EFNB2‑driven tumorigenic effects. These results were further validated in vivo using cell‑derived xenograft models, which confirmed the key role of Wnt/β‑catenin pathway activation in EFNB2‑induced tumor progression. Collectively, these results suggested that EFNB2 represents a promising molecular target for therapeutic intervention in GC.

Following the publication of the above paper, it was drawn to the Editor's attention by an interested reader that the middle and right‑hand protein blots shown for the RIPK4 data in Fig. 2B (relating to the PANC‑1‑Rsh1 and PANC‑1‑Rsh2 experiments) were strikingly similar to western blot data shown in Fig. 3B for the RAF‑1 data (and the same PANC‑1‑Rsh1 and PANC‑1‑Rsh2 experiments), albeit the bands were presented with different exposures/a change in contrast, also with apparent horizontal flipping and vertical resizing. Upon contacting the authors, they realized that errors had been made during the assembly of the experimental images presented in Fig. 3B. These errors were likely to have resulted from oversights made during the process of data consolidation and figure assembly; specifically, this led to the inadvertent use of incorrect images for the RAF‑1 western blot results in both the PANC‑1 cell line (as was correctly identified by the interested reader on PubPeer) and in the Capan‑1 cell line (which the authors identified themselves upon performing their own subsequent review). The authors were also able to present photos of the raw, unedited versions of the gels to the Editorial Office. A revised version of Fig. 3, now showing the correct data for the RAF‑1 blots for both the PANC‑1 and Capan‑1 cell lines, as specified above, is shown on the next page. The authors confirm that the errors made in assembling Fig. 3 did not have a major impact on the conclusions reported in the above article, and they thank the Editor of International Journal of Oncology for allowing them the opportunity to publish a Corrigendum. Furthermore, all the authors agree to the publication of this Corrigendum, and apologize to the readers for any inconvenience caused. [International Journal of Oncology 52: 1105‑1116, 2018; DOI: 10.3892/ijo.2018.4269].

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the westen blot data included in Fig. 4C and D looked strikingly similar, such that the same data may have been included more than once in these figure parts to show the results of differently performed experiments. Upon performing an independent analysis of the data in the Editorial Office, it also came to light that data featured in Fig. 3A of the above paper had been re‑used in a figure in a paper featuring some of the same authors that was published in the journal Scientific Reports. The authors were contacted by the Editorial Office to offer an explanation for this possible anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Oncology 48: 1985‑1996, 2016; DOI: 10.3892/ijo.2016.3404].

Cancer prognostic assessment constitutes an essential component of cancer treatment and management. It encompasses the prediction of patients' disease progression, treatment effect and survival. Circulating free DNA (cfDNA) refers to highly fragmented DNA that exists extracellularly in the human bloodstream. Its methylation status is not only a reliable indicator for the prognosis of cancer, but also a highly accurate predictor of the prognosis of cancer. As an emerging non‑invasive biomarker, cfDNA has demonstrated considerable potential in cancer prognostic assessment in recent years. The present review provided a comprehensive review of the promising applications of cfDNA methylation in cancer prognostic assessment, while also discussing the challenges that must be addressed to fully realize its clinical potential. As technology advances and research deepens, cfDNA methylation is expected to play an increasingly pivotal role in the field of cancer precision medicine.

Germ cell tumors (GCTs) are rare, heterogeneous neoplasms derived from primordial germ cells. Although they typically develop in the gonads, they may also arise in extragonadal locations along the midline of the body. Approximately 90% of patients respond well to cisplatin‑based chemotherapy; however, ~30% exhibit treatment resistance. Epithelial‑mesenchymal plasticity (EMP), a recognized hallmark of cancer, has been implicated in promoting metastasis and chemoresistance. Nonetheless, studies investigating the specific role of EMP in GCT treatment resistance remain limited. The present review compiles key studies on GCTs, EMP markers and cisplatin resistance using both in vitro and in vivo models; it highlights the roles of associated genes, transcription factors and proteins, identifying potential therapeutic targets. Advancing our understanding of EMP and identifying novel therapeutic targets may support the development of treatment strategies that complement or replace cisplatin. This, in turn, could improve survival outcomes and create new avenues for molecular research and clinical applications.

Genome instability is a central hallmark of cancer, driven by aberrant DNA damage responses that facilitate tumor evolution and resistance to therapy. Although canonical non‑homologous end joining and homologous recombination are well‑characterized pathways for repairing DNA double‑strand breaks (DSBs), recent advances have revealed that cancer cells increasingly depend on alternative end‑joining (alt‑EJ) to survive persistent DNA damage that arises from intrinsic stresses or external therapies. Alt‑EJ, characterized by its reliance on microhomologous sequences at DSB sites, promotes mutation accumulation and chromosomal rearrangements, thereby driving genomic instability and tumor progression. Despite its pivotal role in cancer biology, the molecular regulation, contextual determinants and dualistic role of alt‑EJ in maintaining genome integrity compared with promoting instability remain incompletely understood. The present review integrated the latest mechanistic insights into alt‑EJ, elucidated its regulatory networks and interactions with canonical DSB repair pathways and discussed its consequences for cancer genome integrity and evolution. Furthermore, it highlighted the emerging potential of alt‑EJ as a therapeutic vulnerability for cancer, underscoring the urgent need to translate these discoveries into innovative treatment strategies aimed at overcoming therapy resistance and improving patient outcomes.