International journal of oncology最新文献

Osteosarcoma (OS) is a frequently occurring primary bone tumor, mostly affecting children, adolescents and young adults. Before 1970, surgical resection was the main treatment method for OS, but the clinical results were not promising. Subsequently, the advent of chemotherapy has improved the prognosis of patients with OS. However, there is still a high incidence of metastasis or recurrence, and chemotherapy has several side effects, thus making the 5‑year survival rate markedly low. Recently, chimeric antigen receptor T (CAR‑T) cell therapy represents an alternative immunotherapy approach with significant potential for hematologic malignancies. Nevertheless, the application of CAR‑T cells in the treatment of OS faces numerous challenges. The present review focused on the advances in the development of CAR‑T cells to improve their clinical efficacy, and discussed ways to overcome the difficulties faced by CAR T‑cell therapy for OS.

Despite advances in treatment and early detection, breast cancer remains one of the most common types of cancer and is the second leading cause of cancer death after lung cancer in women. Therefore, there is an urgent need to develop new biomarkers and therapeutic targets for the treatment of breast cancer. Based on gene expression profiles and subsequent screening performed in a preliminary study, kinesin family member 20B (KIF20B) was selected as a candidate target molecule, because it was highly and frequently expressed in all subtypes of breast cancer and barely detected in normal tissues. Reverse transcription‑quantitative PCR and western blotting revealed that KIF20B mRNA and protein expression levels were upregulated in most breast cancer cell lines but were scarcely expressed in normal mammary epithelial cells. Immunohistochemical staining of a tissue microarray showed that KIF20B was detected in 145 out of 251 (57.8%) breast cancer tissues. Strong KIF20B expression was significantly related to advanced pathological N stage. Moreover, patients with breast cancer and strong KIF20B expression exhibited a significantly worse prognosis than those with weak or negative KIF20B expression (P<0.0001, log‑rank test). In multivariate analysis, strong expression was an independent prognostic factor for patients with breast cancer. Furthermore, knockdown of KIF20B expression by small interfering RNA inhibited breast cancer cell proliferation and induced apoptosis. In addition, Matrigel cell invasion assays revealed that the invasiveness of breast cancer cells was significantly decreased by KIF20B silencing. Since KIF20B is an oncoprotein that is strongly expressed in highly malignant clinical breast cancer and serves a pivotal role in breast cancer cell proliferation, survival and invasion, KIF20B could be considered a candidate biomarker for prognostic prediction and a potential molecular target for developing new therapeutics, such as small molecule inhibitors, for a wide variety of breast cancers.

Among all types of renal cancer, clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype and is associated with a high risk of metastasis and recurrence. Histone modifications regulate several biological processes that are fundamental to the development of cancer. Lysine methyltransferase 5C (KMT5C; also known as SUV420H2) is an epigenetic modifier responsible for the trimethylation of H4K20, which drives critical cellular events, including genome integrity, cell growth and epithelial‑mesenchymal transition (EMT), in various types of cancer. However, the role of KMT5C in ccRCC remains unclear. As such, the expression and function of KMT5C in ccRCC were investigated in the present study. KMT5C expression was significantly increased in ccRCC tissues compared with normal tissues (P<0.0001), and it was closely associated with the overall survival rate of patients with ccRCC. By establishing ccRCC cell lines with KMT5C expression knockdown, the role of KMT5C in the maintenance of aerobic glycolysis in ccRCC cells via the regulation of several vital glycolytic genes was identified. Additionally, KMT5C promoted the proliferation and EMT of ccRCC cells by controlling crucial EMT transcriptional factors. Together, these data suggested that KMT5C may act as an oncoprotein, guide molecular diagnosis, and shed light on novel drug development and therapeutic strategies for patients with ccRCC.

Lung cancer represents a marked global public health concern. Despite existing treatment modalities, the average 5‑year survival rate for patients with patients with lung cancer is only ~20%. As there are numerous adverse effects of systemic administration routes, there is an urgent need to develop a novel therapeutic strategy tailored specifically for patients with lung cancer. Non‑invasive aerosol inhalation, as a route of drug administration, holds unique advantages in the context of respiratory diseases. Nanoscale materials have extensive applications in the field of biomedical research in recent years. The present study provides a comprehensive review of the classification, applications summarized according to existing clinical treatment modalities for lung cancer and challenges associated with inhalable micron/nanoparticle drug delivery systems (DDSs) in lung cancer. Achieving localized treatment of lung cancer preclinical models through inhalation is deemed feasible. However, further research is required to substantiate the efficacy and long‑term safety of inhalable micron/nanoparticle DDSs in the clinical management of lung cancer.

Chemoresistance is a major challenge in treating triple‑negative breast cancer (TNBC); chemotherapy remains the primary approach. The present study aimed to elucidate the role of guanylate‑binding protein 2 (GBP2) in activating autophagy in TNBC and its impact on the sensitivity of TNBC cells to paclitaxel (PTX). Transfection with lentivirus was performed to establish TNBC cell lines with stable, high GBP2 expression. The mRNA and protein levels of GBP2 expression were evaluated utilizing reverse transcription‑quantitative PCR and western blotting, respectively. Autophagy in TNBC cells was evaluated using immunoblotting, transmission electron microscopy and fluorescence microscopy. The PI3K/AKT/mTOR pathway proteins and their phosphorylation were detected by immunoblotting, and fluorescence co‑localization analysis was performed to evaluate the association between GBP2 and autophagy‑related protein 2 (ATG2). BALB/c NUDE mice were subcutaneously injected with GBP2 wild‑type/overexpressing MDA‑MB‑231 cells. Low GBP2 expression was detected in TNBC, which was associated with a poor prognosis. Overexpression of GBP2 suppressed cell growth, and especially enhanced autophagy in TNBC. Forced expression of GBP2 significantly increased the PTX sensitivity of TNBC cells, and the addition of autophagy inhibitors reversed this effect. GBP2 serves as a prognostic marker and exerts a notable inhibitory impact on TNBC. It functions as a critical regulator of activated autophagy by co‑acting with ATG2 and inhibiting the PI3K/AKT/mTOR pathway, which contributes to increasing sensitivity of TNBC cells to PTX. Therefore, GBP2 is a promising therapeutic target for enhancing TNBC treatment.

Immune checkpoint molecules, such as programmed cell death 1 (PD‑1) and programmed cell death ligand 1 (PD‑L1), have a critical role in regulating immune responses, including in tumor tissues. Monoclonal antibodies against these molecules, known as immune checkpoint inhibitors (ICIs), have been shown to be effective against a variety of cancers; however, significant patient populations are resistant to such treatment. Clinical studies to date have shown that ICIs are less effective in cancer patients with bone metastases. The effect of anti‑PD‑1/PD‑L1 antibodies on bone metastases, as assessed by the bone metastasis‑specific response classification criteria, was relatively low. In addition, the presence of bone metastases showed a trend toward worse progression‑free survival and overall survival in cancer patients treated with ICIs. To improve the efficacy of ICIs in bone metastases, several combination therapies are under investigation and certain studies have reported better responses. The present review summarizes the current understanding of the effects of anti‑PD‑1/PD‑L1 antibodies on bone metastases based on the reported clinical and preclinical studies.

Despite significant advances in oncology, 1 of 108 female patients succumb to ovarian cancer (OC) each year. Improved novel treatments against this aggressive disease would be a major improvement. The growth of OC cells has been demonstrated to be highly dependent on lipids. OC cells are abundantly present in the abdominal cavity and omentum, the main sites of OC expansion. Accordingly, it has been attempted not only to block the hyperactive synthesis of fatty acids (FAs) in cancer cells, but also to disrupt lipid supply. While either strategy has yielded promising results as monotherapy, the induction of resistance pathways diminishing the anticancer effects is yet conceivable. The endogenous regulation of lipid biosynthesis in OC has been extensively studied. However, the role of stromal cells in the modulation of the effects of anti‑lipogenic drugs has not yet been well documented. The present study thus examined the interaction between OC cells and associated stromal cells, when de novo FA synthesis was blocked. It has recently been revealed by the authors that when FA are provided to OC cells in monoculture, the lipid deficiency induced by pharmacological inhibition of FA synthase (FASN), the key enzyme of endogenous FA synthesis, cannot be compensated through an increased FA uptake by OC cells. In the present study, OC cells were co‑cultured with adipocytes preloaded with fluorescent FA and the effects of FASN‑inhibition on OC homing to adipocytes and the transcellular delivery of fluorescent FA from adipocytes to OC cells were examined. The FASN inhibitors, G28UCM and Fasnall, stimulated the spontaneous migration of A2780 OC cells in a concentration‑dependent manner and stimulated the transfer of FA from adipocytes to OC cells. Similar effects were observed with all types of adipocytes tested. The models applied in the present study demonstrated that co‑cultured cancer‑associated adipocytes may attenuate the anticancer effects of FASN inhibitors by attracting tumor cells and by supplying the cells with FA. This lipid‑mediated dependency may provide a rationale for the design of new treatment approaches for the treatment of OC.

Ovarian cancer (OC) is the 5th most common malignancy in women, and the leading cause of death from gynecologic malignancies. Owing to tumor heterogeneity, lack of reliable early diagnostic methods and high incidence of chemotherapy resistance, the 5‑year survival rate of patients with advanced OC remains low despite considerable advances in detection and therapeutic approaches. Therefore, identifying novel therapeutic targets to improve the prognosis of patients with OC is crucial. The expression of glutathione peroxidase 3 (GPX3) plays a crucial role in the growth, proliferation and differentiation of various malignant tumors. In OC, GPX3 is the only antioxidant enzyme the high expression of which is negatively correlated with the overall survival of patients. GPX3 may affect lipid metabolism in tumor stem cells by influencing redox homeostasis in the tumor microenvironment. The maintenance of stemness in OC stem cells (OCSCs) is strongly associated with poor prognosis and recurrence in patients. The aim of the present study was to review the role of GPX3 in OC and investigate the potential factors and effects of GPX3 on OCSCs. The findings of the current study offer novel potential targets for drug therapy in OC, enhance the theoretical foundation of OC drug therapy and provide valuable references for clinical treatment.

Histone modification, a major epigenetic mechanism regulating gene expression through chromatin remodeling, introduces dynamic changes in chromatin architecture. Protein arginine methyltransferase 6 (PRMT6) is overexpressed in various types of cancer, including prostate, lung and endometrial cancer (EC). Epigenome regulates the expression of endogenous retrovirus (ERV), which activates interferon signaling related to cancer. The antitumor effects of PRMT6 inhibition and the role of PRMT6 in EC were investigated, using epigenome multi‑omics analysis, including an assay for chromatin immunoprecipitation sequencing (ChIP‑seq) and RNA sequencing (RNA‑seq). The expression of PRMT6 in EC was analyzed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry (IHC). The prognostic impact of PRMT6 expression was evaluated using IHC. The effects of PRMT6‑knockdown (KD) were investigated using cell viability and apoptosis assays, as well as its effects on the epigenome, using ChIP‑seq of H3K27ac antibodies and RNA‑seq. Finally, the downstream targets identified by multi‑omics analysis were evaluated. PRMT6 was overexpressed in EC and associated with a poor prognosis. PRMT6‑KD induced histone hypomethylation, while suppressing cell growth and apoptosis. ChIP‑seq revealed that PRMT6 regulated genomic regions related to interferons and apoptosis through histone modifications. The RNA‑seq data demonstrated altered interferon‑related pathways and increased expression of tumor suppressor genes, including NK6 homeobox 1 and phosphoinositide‑3‑kinase regulatory subunit 1, following PRMT6‑KD. RT‑qPCR revealed that eight ERV genes which activated interferon signaling were upregulated by PRMT6‑KD. The data of the present study suggested that PRMT6 inhibition induced apoptosis through interferon signaling activated by ERV. PRMT6 regulated tumor suppressor genes and may be a novel therapeutic target, to the best of our knowledge, in EC.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the GAPDH control western blotting assay data shown in Figs. 5D and 6B, the cell‑cycle data in Fig. 4A, the cell apoptotic data in Fig. 4B and the Transwell cell invasion assay in Fig. 3B were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to International Journal of Oncology, or were under consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published previously, the Editor of International Journal of Oncology has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 47: 1594‑1602, 2015; DOI: 10.3892/ijo.2015.3114].