Oncology reports最新文献

Pancreatic cancer is an aggressive tumor, which is often associated with a poor clinical prognosis and resistance to conventional chemotherapy. Therefore, there is a need to identify new therapeutic markers for pancreatic cancer. Although KIN17 is a highly expressed DNA‑ and RNA‑binding protein in a number of types of human cancer, its role in pancreatic cancer development, especially in relation to progression, is currently unknown. The present study verified the upregulation of KIN17 in pancreatic cancer using The Cancer Genome Atlas and Gene Expression Omnibus databases (GSE15471, GSE71989 and GSE62165), and identified an association between the PI3K/Akt/mTOR pathway and patient prognosis using publicly available datasets (Gene Expression Profiling Interactive Analysis). Immunohistochemistry was performed to determine the association between KIN17 and the pathological features of clinical pancreatic cancer samples. Furthermore, knockdown of KIN17 was shown to inhibit the migration and invasion of pancreatic cancer cells, and to reverse epithelial‑mesenchymal transition in pancreatic cancer cells through downregulation of Vimentin and N‑cadherin, and upregulation of E‑cadherin. Through various cellular experiments, the role of KIIN17 was explored in PI3K/AKT/mTOR activity. KIN17 inhibition was shown to suppress the migration and invasion of pancreatic cancer cells through PI3K/AKT/mTOR‑mediated autophagy. Furthermore, combined with mTOR inhibition, dual inhibition could enhance autophagy, leading to anti‑migratory and anti‑invasion effects in pancreatic cancer. In conclusion, the present study indicated that KIN17 may have a role in carcinogenesis and could serve as a prognostic biomarker of pancreatic cancer, owing to its high expression. In addition, KIN17 may be considered a potential therapeutic target with its knockdown having an inhibitory effect on pancreatic cancer.

RUVBL1 is a protein characterized by its DNA‑dependent ATPase activity and DNA deconjugating enzyme function. It is a member of the ATPase (AAA+) protein family associated with various cellular processes. Available research confirms that the expression of RUVBL1 is upregulated in breast cancer (BRCA) cell lines; however, the mechanisms underlying its functional role in BRCA remain unclear. The β‑catenin/lymphoid enhancer factor‑1 (LEF‑1) pathway plays a crucial role in the occurrence and development of BRCA. The aim of the present study was to investigate whether RUVBL1 regulates the proliferation, migration and invasion of BRCA cells by participating in the β‑catenin/LEF‑1 signaling pathway. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis were employed to compare the RUVBL1 expression levels between normal mammary epithelial cells (MCF‑10a) and BRCA cell lines (MDA‑MB‑231 and MCF‑7). Scratch, Cell Counting Kit‑8 and Transwell assays were utilized to assess the effects of RUVBL1 knockdown on the proliferation, migration and invasion of BRCA cells. Following the downregulation of RUVBL1 expression in vitro, western blot analysis and RT‑qPCR were conducted to investigate its role in regulating the β‑catenin/LEF‑1 pathway. The aforementioned experiments proved that the knockdown of RUVBL1 expression inhibited BRCA cell proliferative, migratory and invasive capabilities, modulating the β‑catenin/LEF‑1 pathway. Collectively, the findings of the present study provide preliminarily confirmation that RUVBL1 participates in the molecular mechanisms of the β‑catenin signaling pathway, which may provide a novel target for BRCA treatment.

Esophageal cancer (ESCA) is a common tumor noted in the digestive tract, which is highly malignant due to unclear early symptoms and poor last‑stage treatment effects; its mortality rate is relatively high. MicroRNA (miR) and signal transducer and activator of transcription 3 (STAT3) are key components of cellular signaling pathways; their interaction forms a complex and intricate information network that controls several types of biological behaviors in the cells. In the tumor cell, these signal transduction pathways are abnormally active, indicating that the STAT3 signaling pathway mediated by miRs is involved in the progression of various cancer types. The present review introduces the biological characteristics of miR and STAT3 and their relationship with ESCA. It summarizes the regulation of ESCA by the miR and STAT3 signaling pathways and analyzes the effects of these pathways on proliferation, apoptosis, invasion, metastasis and immune escape of cancer cells, as well as the impact on patient survival and prognosis. The purpose of the present review is to assess the miR/STAT3 signaling pathway in ESCA, improve the understanding of the pathogenesis of ESCA and facilitate the identification of therapeutic targets for ESCA.

Non‑small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite significant advances in targeted therapy and immunotherapy, the overall prognosis of patients with NSCLC remains poor. Hypoxia is a critical driving factor in tumor progression, influencing the biological behavior of tumor cells through complex molecular mechanisms. The present review systematically examined the role of the hypoxic microenvironment in NSCLC, demonstrating its crucial role in promoting tumor cell growth, invasion and metastasis. Additionally, it has been previously reported that the hypoxic microenvironment enhances tumor cell resistance by activating hypoxia‑inducible factor and regulating exosome secretion. The hypoxic microenvironment also enables tumor cells to adapt to low oxygen and nutrient‑deficient conditions by enhancing metabolic reprogramming, such as through upregulating glycolysis. Further studies have shown that the hypoxic microenvironment facilitates immune escape by modulating tumor‑associated immune cells and suppressing the antitumor response of the immune system. Moreover, the hypoxic microenvironment increases tumor resistance to radiotherapy, chemotherapy and other types of targeted therapy through various pathways, significantly reducing the therapeutic efficacy of these treatments. Therefore, it could be suggested that early detection of cellular hypoxia and targeted therapy based on hypoxia may offer new therapeutic approaches for patients with NSCLC. The present review not only deepened the current understanding of the mechanisms of action and role of the hypoxic microenvironment in NSCLC but also provided a solid theoretical basis for the future development of precision treatments for patients with NSCLC.

Laryngeal squamous cell carcinoma (LSCC), which represents a significant proportion of head and neck squamous cell carcinoma cases, is often diagnosed at advanced stages, underscoring the urgent need for effective biomarkers and therapeutic targets. Junctional adhesion molecule 3 (JAM3) is implicated in various types of cancer; however, its role in LSCC remains unclear. Therefore, the present study aimed to investigate the epigenetic regulation and tumor‑suppressive functions and mechanisms of JAM3 in LSCC. Bioinformatics analysis and 5‑Aza‑2'‑deoxycytidine treatment, which restored JAM3 expression as confirmed by reverse transcription‑quantitative PCR and western blotting, revealed that aberrant hypermethylation of the JAM3 promoter was associated with reduced JAM3 expression and poorer clinical outcomes in patients with LSCC. In vitro experiments, including Cell Counting Kit 8, colony formation and Transwell assays, demonstrated that JAM3 overexpression inhibited LSCC cell proliferation, migration and invasion. Western blotting and immunofluorescence analysis revealed that the tumor‑suppressive function of JAM3 was mediated through activation of the Hippo pathway. By contrast, both in vitro and in vivo experiments showed that JAM3 knockdown enhanced these oncogenic behaviors by inhibiting the Hippo pathway, suggesting its critical tumor‑suppressive role. In conclusion, the results of the present study indicated that JAM3 may be epigenetically downregulated and could function as a novel tumor suppressor gene through the Hippo pathway in LSCC, offering insights into developing targeted treatments and diagnostics.

The global incidence of prostate cancer (PCa) is rising. Localized PCa can be managed through surgical intervention or radiotherapy, but certain patients may experience recurrence or develop metastatic disease following localized treatment. Despite aggressive therapeutic approaches, the majority of metastatic patients with PCa will eventually progress to metastatic castration‑resistant PCa, with limited treatment alternatives and a dismal prognosis. The treatment options for advanced PCa are continuously evolving, yet there remains a demand for further innovative therapeutic approaches. Antibody‑drug conjugates (ADCs) represent a novel class of targeted medications comprising a humanized monoclonal antibody, a linker and a cytotoxic payload. ADCs primarily bind to antigens that are upregulated on the surface of PCa cells but are minimally expressed on normal cells. At present, a variety of targets for ADCs have been identified in the treatment of PCa, encompassing prostate‑specific membrane antigen, STEAP family member 1, trophoblast cell‑surface antigen 2, CD46, B7‑H3, tissue factor and delta‑like protein 3, each with one or more specific ADC that has shown encouraging results in the PCa field. In the present review, the developmental course, composition and mechanism of action of ADCs are explored, with a specific focus on recently published studies and ongoing trials aimed at investigating the efficacy and safety of ADCs in treating PCa. Lastly, ongoing challenges in ADC development and corresponding strategies to combat them are discussed.

Targeted drugs have revolutionized the treatment of advanced non‑small cell lung cancer (NSCLC). However, the understanding of how cardiac comorbidity and toxicity affect the clinical outcomes of patients following targeted therapy remains limited. In a 14‑year cohort, cardiac comorbidities and toxicities among patients with stage‑IV NSCLC treated with targeted therapy were identified. The cardiotoxicities were compared in three patient groups: Cardiac, other and no comorbidities. Survival analysis employed Cox Proportional Hazard Models. In the prospectively followed 3,767 patients with stage‑IV NSCLC, 701 received targeted therapy; of which 133 (19.0%) had cardiac comorbidity, 504 (71.9%) had other comorbidities and 64 (9.1%) had none. In total, 15 patients (2.1%) developed cardiotoxicity after taking drugs targeting epidermal growth factor receptor, anaplastic lymphoma kinase (ALK), c‑ros oncogene 1 (ROS1) or vascular endothelial growth factor/receptor (VEGF)/VEGFR, and all 15 had comorbidities: 10 cardiac and 5 other comorbidities. Cardiac comorbidity was associated with a 7.5‑fold higher risk of targeted therapy‑related cardiotoxicity than other comorbidities (7.5 vs. 1.0%; P<0.001). Patients with or without cardiotoxicity had a median survival time of 4.7 or 1.9 years, respectively, and patients with cardiotoxicity had a lower risk of death (hazard ratio, 0.45; 95% confidence interval, 0.25‑0.81) than those without (P=0.003), when adjusting for comorbidities. In the 164 patients that received osimertinib, 32 (19.5%) had cardiac comorbidity and a 1.7‑fold higher risk of death than the 121 (73.8%) patients with other comorbidities. In the 74 patients treated with ALK/ROS1 inhibitors, cardiotoxicity was 14 times more common in patients with heart disease (30.0%) than those without (2.1%) (P=0.001). Cardiotoxicity was uncommon in patients with targeted drug‑treated stage‑IV NSCLC but was more prevalent in those with cardiac comorbidity and appeared to be a protector for longer survival. However, in osimertinib‑treated patients, cardiac comorbidity increased mortality.

Ferroptosis is a form of programmed cell death that is distinct from apoptosis. The mechanism involves redox‑active metallic iron and is characterized by an abnormal increase in iron‑dependent lipid reactive oxygen species, which results in high levels of membrane lipid peroxides. The relationship between ferroptosis and gynaecological tumours is complex. Ferroptosis can regulate tumour proliferation, metastasis and chemotherapy resistance, and targeting ferroptosis is a promising antitumour approach. Ferroptosis interacts with mechanisms related to tumorigenesis and development, such as macrophage polarization, the neutrophil trap network, mitochondrial autophagy and cuproptosis. The present review examines recent information on the interaction between the molecular mechanism of ferroptosis and other tumour‑related mechanisms, as well as the involvement of ferroptosis in gynaecological tumours, to identify implications for gynaecological cancer therapy.

Cancer stem cells (CSCs) have been implicated as critical mediators in the progression, chemoresistance and metastatic capabilities of diverse malignancies, including osteosarcoma (OS). The authors have succeeded in generating CSC‑like cells (MG‑OKS) from the OS cell line MG‑63 by transducing defined factors. A significant increase in small proline‑rich protein 1A (SPRR1A) expression, a cross‑linked envelope protein in keratinocytes, was observed in MG‑OKS cells. Therefore, SPRR1A could be involved in tumor initiation, growth and poor OS progression. However, its specific role in OS remains unclear. The present study aimed to evaluate the role of SPRR1A in OS both in vitro and in vivo using MG‑OKS cells. Three experimental groups were established: MG‑OKS cells transfected with SPRR1A small interfering (si)RNA (siMG‑OKS), untransfected MG‑OKS cells and MG‑OKS cells transfected with scrambled siRNA (scMG‑OKS) as controls. SPRR1A expression, morphological changes, cell proliferation and migration were assessed in these groups. RNA sequencing was performed to examine the genetic changes caused by SPRR1A suppression. To evaluate tumorigenicity in vivo, cells from each group were subcutaneously transplanted into the backs of nude mice. Tumor volume and Ki‑67 expression were assessed and compared among the three groups at four weeks post‑transplantation. The siMG‑OKS group exhibited altered cell morphology, reduced cell proliferation and decreased migratory abilities in vitro. RNA sequencing revealed suppression of genes involved in cell adhesion in the siMG‑OKS group. Furthermore, the in vivo tumorigenicity of siMG‑OKS was lower than that of the other two experimental groups. These findings suggest that SPRR1A is one of the key cell adhesion‑related molecules involved in OS progression, potentially serving as a therapeutic target for this refractory tumor. However, further research is needed to fully elucidate the mechanisms by which SPRR1A influences OS pathogenesis and to explore its clinical potential.

Following the publication of the above article, a concerned reader drew to the Editor's attention that a couple of the figures in this paper contained overlapping sections, where data which were intended to show the results from differently performed experiments had been derived from the same original source. First, regarding the cell transfection experiments in Fig. 1, the Con, ERα and ERβ data panels in Fig. 1A all contained overlapping sections of data; secondly, comparing the data panels for the cell migration and invasion assays shown in Fig. 5, three pairs of panels were also found to contain overlapping data. In view of the fact that these identifications were made in terms of overlapping data panels, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 31: 1175‑1182, 2014; DOI: 10.3892/or.2013.2944].