Oncology reports最新文献

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Fig. 4B were remarkably similar to the data shown in Fig. 2B for the CAL‑27 experiments, albeit the panels in the latter figure were shown rotated through 90/180° relative to the former figure. Moreover, upon performing an independent analysis of the data in the Editorial Office, it came to light that some of the flow cytometric data in Fig. 2C were strikingly similar to data that had appeared previously in an article in the journal Oncology Letters that was written by different authors at different research institutes. Given that the contentious data in the above paper had apparently already been published in an unrelated article prior to its submission to Oncology Reports, the Editor 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 reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 34: 2961‑2968, 2015; DOI: 10.3892/or.2015.4323].

Glioblastoma (GBM), the most common type of primary malignant brain tumor, is characterized by aggressive cancer cells that contribute to infiltrative growth, thus resulting in therapeutic challenges and a poor prognosis. To explore the molecular mechanisms underlying cell motility and to identify therapeutic targets that may intervene in tumor invasion, public databases were used to investigate the S100B expression profile and the prognosis of patients with tumors. The effects of S100B on a GBM cell line were assessed through lentiviral transduction, as well as cell viability, colony formation, 5‑ethynyl‑2'‑deoxyuridine‑based cell proliferation, cross‑scratch, and Transwell migration and invasion assays. In addition, a tumor xenograft model was constructed to analyze tumor growth in vivo. Reverse transcription-quantitative PCR, western blotting and immunofluorescence staining were utilized to explore the molecular biological mechanisms of the TGF‑β2‑induced epithelial‑mesenchymal transition (EMT) in the S100B‑downregulated group. The findings demonstrated that S100B was significantly upregulated in GBM samples and was strongly associated with patient prognosis. In vitro and in vivo experiments confirmed that downregulation of S100B effectively suppressed the proliferation and tumorigenicity, as well as decreased the invasive and migratory capabilities of LN229 glioblastoma cells. Further investigation revealed that the inhibition of S100B resulted in downregulation of TGF‑β2 expression and reversal of the EMT process. Notably, recombinant TGF‑β2 restored the cell motility and EMT capacities attenuated by the downregulation of S100B. In conclusion, the present study revealed that S100B may induce the invasion and migration of GBM cells through TGF‑β2‑induced EMT, providing novel insights and potential therapeutic targets for GBM.

CD44 serves a dual role in supporting tumor survival and promoting invasion. Claudin‑low breast cancer, characterized by a CD44⁺/CD24^‑ phenotype and epithelial‑mesenchymal transition (EMT), displays aggressive behavior. The present study investigated the interaction between CD44 and TGF‑β signaling, and assessed the cellular effects of their combined inhibition. CD44 was knocked down in claudin‑low breast cancer cell lines (SUM159 and MDA‑MB‑231), and the TGF‑β receptor (TGFBR) inhibitor LY2109761 (LY‑61) was applied for treatment. Cell viability (MTT assay), apoptosis (annexin V assay), invasion (Transwell assay), colony formation and Smad2 phosphorylation (western blotting) were evaluated. CD44 knockdown reduced viability and increased apoptosis but did not markedly suppress invasion. Although TGF‑β stimulation enhanced Smad2 phosphorylation, CD44 knockdown alone did not increase Smad2 activation, indicating that it does not directly regulate Smad2. However, LY‑61 inhibited TGF‑β‑induced Smad2 phosphorylation, effectively counteracting pro‑invasive signaling. Notably, while CD44 knockdown alone had a negligible impact on invasion, its combination with LY‑61 markedly reduced the invasive capacity and colony formation of cells compared with the control (control cells transduced with non‑targeting short hairpin RNA without LY‑61 treatment). LY‑61 induced S phase accumulation, which was more pronounced in SUM159 cells than in MDA‑MB‑231 cells, indicating cell line‑specific effects on cell‑cycle regulation. Clinical data indicated that low CD44 expression was associated with improved survival in patients with claudin‑low breast cancer, despite its potential to enhance EMT signaling. These findings suggested that CD44 knockdown enhanced the response to TGFBR inhibition. Although CD44 depletion may increase EMT‑related signaling, invasion was primarily suppressed by TGF‑β blockade, and the combination with CD44 knockdown further enhanced the inhibition of proliferative phenotypes compared with either treatment alone. This dual‑targeting approach warrants further investigation in claudin‑low breast cancer.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that cell invasion and migration assay data featured in Fig. 5C on p. 1164 were strikingly similar to data that already been submitted for publication to the journal Oncology Letters in a paper written by different authors at different research institutes. Moreover, cell invasion and migration assay data panels both within Fig. 6C, and comparing Fig. 6C with Fig. 5C, revealed a number of internally overlapping panels, suggesting that data which were intended to have shown the results from differently performed experiments had apparently been derived from a smaller number of original sources. Owing to the fact that the abovementioned data had already been submitted for publication prior to the receipt of this article at Oncology Reports, the Editor 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. [Oncology Reports 37: 1159‑1167, 2017; DOI: 10.3892/or.2016.5320].

Leucine‑rich repeat‑containing protein 59 (LRRC59), a 244‑amino‑acid endoplasmic reticulum membrane protein, is implicated in the tumorigenesis of multiple malignancies. However, its functional significance in colorectal cancer (CRC) remains poorly understood. In the present study, LRRC59 expression in CRC tissues was evaluated using immunohistochemistry and western blotting. Colony formation, Cell Counting Kit‑8, wound healing and Transwell assays, in in vivo xenograft models, were used to evaluate the effect of LRRC59 on CRC progression. Apoptosis was analyzed using flow cytometry and western blotting. The interaction between LRRC59 and the protein kinase RNA‑like endoplasmic reticulum kinase (PERK) pathway was verified using the starBase database and western blotting. It was found that LRRC59 expression was significantly higher in CRC tissues than in normal tissues. LRRC59 knockdown in HCT116 and LoVo cells inhibited proliferation, migration and invasion and promoted apoptosis, and the PERK pathway was significantly activated. In vivo subcutaneous tumorigenesis assays corroborated these in vitro findings. Treatment with a PERK pathway‑specific inhibitor reduced the apoptosis of HCT116 and LoVo cells with LRRC59 knockdown. These findings suggest that LRRC59 is not only significantly upregulated in CRC but also mechanistically drives tumor progression by coordinating pro‑oncogenic processes, including enhanced proliferation, migration and invasion. Importantly, mechanistic evidence was provided that LRRC59 inhibits apoptosis by suppressing the PERK signaling axis, identifying this molecule a target in the development of CRC therapeutic strategies.

Treatment options for triple‑negative breast cancer (TNBC) are limited because they typically harbor a high cancer stem‑like population and exhibit a relatively aggressive metastatic phenotype. Heat shock protein 90 (HSP90), a molecular chaperone that regulates diverse oncogenic client proteins, has emerged as a compelling therapeutic target owing to its involvement in key tumor‑promoting processes, such as uncontrolled proliferation, angiogenesis and metastasis. Owing to the undesirable induction of a compensatory heat shock response (HSR) and systemic toxicity, classical N‑terminal inhibitors of HSP90 have failed in clinical trials. The impact of a rationally designed novel inhibitor of the HSP90 C‑terminus in TNBC cells was investigated. NCT‑58 eliminates rapidly proliferating tumor cells accompanied by simultaneous degradation of AKT, MEK and STAT3, and effectively eradicates the cancer stem‑like population (breast cancer stem cells) in both human MDA‑MB‑231 and murine 4T1 cells. The latter phenomenon is accompanied by reductions in the activity of ALDH1 and the CD44^high/CD24^low stem‑like population, as well as impairment of mammosphere formation. Furthermore, NCT‑58 markedly impairs cell migration, coinciding with the collapse of HSP90 client cytoskeletal proteins, including vimentin and F‑actin, in MDA‑MB‑231 cells in vitro. A synergistic effect was observed when NCT‑58 was combined with paclitaxel or doxorubicin in MDA‑MB‑231 cells. Collectively, these findings indicated that targeting the C‑terminal domain of HSP90 with NCT‑58 is a promising therapeutic strategy for the treatment of molecularly heterogeneous TNBC.

Leukemia is a group of hematologic malignancies characterized by the uncontrolled proliferation of abnormal white blood cells, posing significant challenges for diagnosis and treatment because of its complex etiology. Both genetic and environmental factors contribute to leukemogenesis, with recent research highlighting the critical role of epigenetic modifications, particularly histone acetylation and deacetylation, in regulating gene expression and disease progression. Dysregulation of histone deacetylases (HDACs) is frequently observed in leukemia and is correlated with poor prognosis and resistance to conventional therapies. This observation has led to the development of epigenetic drugs for leukemia treatment. The emergence of HDAC inhibitors (HDACis) as targeted therapeutics offers promising avenues for more selective and effective leukemia treatments. The present review covers basic aspects of histone modification and its role in leukemogenesis and evaluates the potential of peptide‑based HDACis as novel drugs for leukemia therapy.

Mebendazole (Mbz), a well‑known anthelminthic drug, has demonstrated anticancer properties in tumor models and patients, and is thus under consideration for repositioning into an anticancer drug. Mbz is directly cytotoxic in cell lines by various mechanisms and acts indirectly via immunomodulation. In the present study, the anticancer effects of Mbz, alone and in combination with cytotoxic drugs, were further characterized using primary cultures of patient tumor cells ex vivo and the murine colon cancer cell line, CT26, in vitro and in vivo. Patient‑derived tumor cells from acute myeloid leukemia (AML) and ovarian, colorectal and renal cancer were exposed to Mbz alone and, for solid tumors and the CT26 cell line, in combination with irinotecan, cisplatin or gemcitabine (patient cells only). Cytotoxicity was assessed using the fluorometric microculture cytotoxicity assay. In vivo, the antitumor effects of Mbz and irinotecan, alone and in combination, were evaluated in the BALB/c CT26 colon cancer mouse model by tumor growth measurements and flow cytometric analysis of tumor immune cell infiltration. In the patient cell samples, Mbz showed modest single‑agent cytotoxicity, with the AML samples being the most sensitive, and displayed enhanced effects when combined with cytotoxic drugs, particularly irinotecan. CT26 cells showed modest dose‑independent sensitivity to Mbz, which enhanced the effect of both cisplatin and irinotecan. In vivo, Mbz and irinotecan both inhibited tumor growth, but the combination did not significantly outperform Mbz alone. Flow cytometry of the resected mouse tumors indicated that Mbz promoted macrophage polarization from the M2 to M1 phenotype, suggesting that immune modulation may contribute to its anticancer effect. Mbz has features making it a candidate for repositioning into an anticancer drug and part of its effect may be mediated by macrophage modulation.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, concerning the  flow cytometric plots featured in Fig. 3A‑C on p. 1215, certain groups of data points appeared more similar to each other than might be expected. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. Therefore, 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 Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 35: 1213‑1221, 2016; DOI: 10.3892/or.2015.4443].

Breast cancer (BC) ranks among the most prevalent malignant tumors in female patients. It represents a longstanding challenge to medical professionals in terms of diagnosis and treatment. Exploring BC pathogenesis offers insight into its complexity and facilitates the exploration of more effective treatment strategies. The present review aimed to describe the involvement of the immune system, inflammatory response and regulated cell death in BC development, offering avenues for novel therapeutic strategies against BC. Identifying novel treatment methods is key for enhancing the prognosis of patients with BC.