Oncology reports最新文献

Carcinoma‑associated fibroblasts (CAFs) exhibit notably heterogeneity and are closely implicated in immune checkpoint blockade (ICB) resistance in head and neck squamous cell carcinoma (HNSCC). However, the specific subtypes and mechanisms involved remain to be elucidated. By analyzing two single‑cell RNA sequencing datasets (GSE103322 and GSE139324) and The Cancer Genome Atlas (TCGA)‑HNSCC dataset, two distinct fibroblasts subtypes were identified: Perostin (POSTN)^‑ and POSTN⁺ fibroblasts. A comparison with reported markers revealed that extracellular matrix‑related markers were highly expressed in POSTN⁺ fibroblasts. In addition, fibroblast activation protein and POSTN expression were positively associated with macrophage infiltration and predicted ICB resistance in TCGA‑HNSCC dataset. Immunogold labeling confirmed the enrichment of POSTN on the membrane surface of CAF‑derived small extracellular vesicles (sEVs) and it was indicated that these POSTN⁺ sEVs may promote THP‑1‑derived macrophages polarization toward the M2 phenotype. Additionally, sEVs derived from CAFs with POSTN knockdown reduced bone morphogenetic protein (BMP) 4 expression in macrophages, thereby inhibiting M2 polarization through the BMP receptor 2/Smad pathway. Collectively, these findings revealed that a POSTN⁺ fibroblasts fosters an immunosuppressive microenvironment via sEV‑mediated macrophage polarization, nominating POSTN as a potential therapeutic target to overcome ICB resistance in HNSCC.

Breast cancer is a global health challenge for women and chemoresistance is a major contributor to its high mortality rates. Quercetin (Que), a flavonoid with antioxidant, antiviral, anti‑tumor and anti‑inflammatory properties, sensitizes cancer cells to chemotherapy. The present study investigated the mechanism by which Que regulates ATP‑binding cassette (ABC) transporter expression in MCF‑7 cells using a PTEN overexpression plasmid and the PI3K inhibitor LY294002. The present study assessed cell viability via Cell Counting Kit‑8 and Hoechst 33342 staining and analyzed mRNA and protein expression levels by reverse transcription‑quantitative PCR and western blotting. Apoptosis was evaluated by flow cytometry and ABCG2 expression was detected by immunofluorescence. Furthermore, the present study determined the effect of Que on drug uptake using a Rhodamine 123 accumulation assay. The results of the present study demonstrated that Que suppresses cell viability and induces apoptosis in MCF‑7 cells. Moreover, it enhances intracellular drug accumulation and downregulates ABC transporter expression by modulating the PTEN/PI3K/AKT signaling pathway.

Triple‑negative breast cancer (TNBC) is a highly malignant subtype with limited effective treatment options. The present study investigated the antitumor immune effects of mifepristone, a glucocorticoid receptor antagonist, using subcutaneous, orthotopic and experimental lung metastasis mouse models transplanted with 4T1 TNBC cells. Mifepristone treatment suppressed tumor growth and metastasis, leading to improved overall survival. Flow cytometric analysis of the spleen revealed decreased polymorphonuclear myeloid‑derived suppressor cells (PMN‑MDSCs) and increased T cells in the spleen, accompanied by enhanced T‑cell activity assessed ex vivo. Similar immune alterations were observed in tumor‑infiltrating cells, indicating enhanced intratumoral T‑cell responses. These results suggested that the antitumor effects of mifepristone may be partly mediated by reducing PMN‑MDSCs and restoring antitumor immunity. In tumor‑bearing mice, plasma levels of corticosterone, the major murine glucocorticoid, were elevated. In in vitro experiments using bone marrow and splenocytes, corticosterone promoted PMN‑MDSC induction and suppressed T‑cell activity, and these effects were reversed by mifepristone. Thus, mifepristone may modulate immune cell dynamics by inhibiting systemic corticosterone. To elucidate the mechanism underlying plasma corticosterone elevation, the corticosterone‑generating capacity of 4T1 cells was analyzed by exposing them to 11‑dehydrocorticosterone (DHC). The results demonstrated that 4T1 cells possessed the ability to convert the inactive form of glucocorticoid, DHC, into its active form, corticosterone, through the enzymatic activity of 11β‑hydroxysteroid dehydrogenase type 1 (11β‑HSD1). Furthermore, treatment with carbenoxolone (a non‑selective 11β‑HSD1 inhibitor) in tumor‑bearing mice decreased plasma corticosterone levels, suppressed tumor growth and produced immune changes similar to mifepristone treatment. These findings suggested that the elevated plasma corticosterone levels in tumor‑bearing mice may be mediated by 11β‑HSD1‑dependent corticosterone production, and that this mechanism was likely induced by 4T1 cells. In conclusion, the present study indicated that 4T1 cells possess corticosterone‑generating capacity through 11β‑HSD1, promoting systemic corticosterone elevation and tumor growth. Mifepristone may restore antitumor immunity, likely by reducing PMN‑MDSCs through systemic corticosterone blockade. These insights could inform the development of novel therapeutic approaches for TNBC.

Following the publication of the above article and a corrigendum (doi: 10.3892/or.2022.8264) that was published 3 years ago to resolve the issue of two sets of duplicated western blots in Fig. 3, an interested reader drew to the authors' attention that, in Fig. 5b on p. 2441, the western blot data bands shown to represent the GRP78 and Bcl‑2 proteins in the MCF‑7 group were strikingly similar; furthermore, the β‑actin bands shown for the MDA‑MB‑231 group in Fig. 5c were strikingly similar to the β‑actin bands shown in Fig. 2c on p. 2439. After having re‑examined their original data, the authors realized that the figure parts in question were inadvertently assembled erroneously. The revised version of Fig. 5, now featuring the correct data for the GRP78 western blot bands for the MCF‑7 group in Fig. 5b and the β‑actin bands in Fig. 5c, is shown in the next page. Note that the errors made in assembling this figure did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for granting them the opportunity to publish this; furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 40: 2435‑2444, 2018; DOI: 10.3892/or.2018.6644].

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in comparing Figs. 1A and 2B, which both showed the results of invasion assay experiments, the 'Normoxia / U87' data panel in Fig. 1A appeared to overlap with the 'CCR5 siRNA' panel in Fig. 2B, whereas the 'Hypoxia / U87‑Mφ' panel in Fig. 1A also appeared to overlap with the 'Control siRNA' panel in Fig. 2B [also note that an expression of concern statement (doi.org/10.3892/or.2025.8989) was issued for this paper]. The authors were able to re‑examine their original data files, and realized that the images for Fig. 2B had been inadverently selected incorrectly. The revised version of Fig. 2, containing the correct data for the invasion assay experiments in Fig. 2B, is shown on the next page. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 36: 3522‑3528, 2016; DOI: 10.3892/or.2016.5171].

Following the publication of the above article, it was drawn to our attention by a concerned reader that the pairs of data panels showing the results for the Paxitaxel (or Epirubicin) + Lapatinib and the Paxitaxel (or Epirubicin) + Trastuzumab experiments respectively in Fig. 2E on p. 774 were overlapping, such that data which were intended to show the results from differently performed experiments had apparently been derived from the same original sources. After having further investigated the data in this paper in the Editorial Office, it was also identified that certain Transwell assay data were shared comparing Fig. 1D with Fig. 2E, and several of the western blot control experimental data were shared between Figs. 1A‑C and 2A‑C, although it wasn't entirely clear whether these data were intended to have portrayed the same experimental results in these figures. More importantly, examining the immuno-histochemical assay data in Fig. 3A and B, two pairs of data panels were found to be overlapping, where these figure parts were described in the legend as relating to mouse and human experiments respectively; therefore, different experimental data presumably should have been presented for Fig. 3A and B in this figure. The authors requested that a corrigendum be published to present the data in Fig. 2 (initially) accurately. The Editor of Oncology Reports has considered the authors' request to publish a corrigendum, but has decided to decline this request on account of the additional errors that have been identified in the assembly of data in (at least) Fig. 3 in this paper; rather, the article is to be be retracted from the Journal on account of an overall lack of confidence in the presented data. The authors were asked for an explanation to account for these additional concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership of the Journal for any inconvenience caused. [Oncology Reports 35: 771‑778, 2016; DOI: 10.3892/or.2015.4444].

Circulating tumor cells (CTCs) are shed from the primary tumor into the peripheral bloodstream, where they play crucial roles in tumor metastasis and recurrence. As a cornerstone of liquid biopsy, CTCs hold significant potential for early tumor diagnosis, therapeutic response monitoring, and prognosis. However, the rarity and heterogeneity of CTCs pose considerable challenges for their isolation and enrichment. Additionally, their predictive usefulness in tumor immunotherapy remains relatively limited. The present review summarizes recent advancements in CTC isolation and detection technologies, explores their clinical applications in immunotherapy, and discusses current challenges alongside potential strategies for improvement. The integration of these technologies into clinical practice could pave the way for more personalized and precise cancer treatment strategies in the future.

Mitochondria are central to cellular metabolic reprogramming, and their energy metabolism pathways are indispensable for T‑cell activation, proliferation and differentiation. Mitochondrial metabolic reprogramming enhances T‑cell activity and antitumor function. Mitochondrial dynamics, including fusion, fission and transfer, regulate T‑cell tumor immune function by modulating the number, morphology and distribution of mitochondria, which is vital for the antitumor effects of T cells. The release of mitochondrial DNA can activate multiple innate immune signaling pathways, such as cyclic GMP‑AMP synthase‑stimulator of interferon genes, Toll‑like receptor 9, and NOD‑, LRR‑, and pyrin domain‑containing protein 3, serving a complex regulatory role in shaping the tumor immunosuppressive microenvironment and T‑cell antitumor immune responses. Notably, mitochondrial dysfunction is a major driver of tumor initiation and progression. T‑cell mitochondrial metabolic reprogramming, dynamic changes and mitochondrial DNA release all affect the antitumor immunity of tumor‑infiltrating T cells. The present review focuses on the relationship between mitochondria and T‑cell antitumor immune responses, exploring the core role of mitochondria in T‑cell tumor immunity from multiple aspects, including mitochondrial energy metabolism, mitochondrial dynamics and mitochondrial DNA. In addition, the present review examines state‑of‑the‑art research on antitumor therapies targeting mitochondria from multiple perspectives, with the aim of providing a reference for developing mitochondria‑targeted antitumor immunotherapy strategies.

Following the publication of the above article, a concerned reader drew to the Editor's attention that there were anomalies associated with the Transwell data shown in Figs. 2B and C and 5A‑D; essentially, groupings of cells appeared to be markedly similar in appearance looking within various of the data panels in these figures. After having conducted an internal investigation of the data in this paper, the Editor of Oncology Reports has judged that the potentially anomalous presentation of the strikingly similar groupings of cells in Figs. 2 and 5 were too extensive that these features could have been attributed to pure coincidence. Therefore, the Editor has decided that this article should be retracted from the publication on the grounds of an overall lack of confidence in the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor sincerely apologizes to the readership for any incovenience caused, and we thank the reader for bringing this matter to our attention. [Oncology Reports 39: 255‑263, 2018; DOI: 10.3892/or.2017.6079].

DNA replication stress and energy homeostasis are critical yet underexplored pathways in prostate cancer (PCa). Identifying PCa prognostic biomarkers associated with these pathways are essential for advancing diagnostics and treatment. The present study aimed to analyze transcriptomic and clinical data from public datasets to identify DNA replication stress and energy homeostasis‑related genes associated with PCa. Biomarkers were assessed using reverse transcription‑quantitative (RT‑q) PCR, western blotting and consistent expression trends across datasets. Survival analyses evaluated the effect of biomarkers on clinical outcomes, while immune microenvironment changes and immunotherapy responses were evaluated. Mutation and drug sensitivity analyses explored genetic variations and chemotherapy efficacy. Functional assays, including cell proliferation, migration, RT‑qPCR and western blotting, confirmed biomarker roles in PCa progression. RecQ mediated genome instability 1 (RMI1) was identified as a novel biomarker, consistently upregulated in PCa tissues across datasets and experiments (P<0.05). High RMI1 expression was associated with worse survival outcomes, advanced clinical stages, immune escape and TP53 mutations. Enrichment analysis linked RMI1 to cell cycle, DNA replication and metabolic pathways. Functional assays revealed that RMI1 knockdown inhibited PCa cell proliferation and migration, suggesting its role in tumor progression. Additionally, high RMI1 expression was associated with resistance to certain chemotherapeutic agents, such as irinotecan. These results underscored RMI1 as a promising prognostic biomarker and a potential therapeutic target for the management of PCa. In conclusion, the present study identified RMI1 as a biomarker for the detection of PCa and may promote cancer cell progression by promoting proliferation and migration.