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Journal of Oncology publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.
Journal of Oncology maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.
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Correlation between FAK and EGF-Induced EMT in Colorectal Cancer Cells
Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and metastasis of colorectal cancer, which is mediated by FAK and EGF. However, whether FAK participates in EMT in colorectal cancer cells through the EGF/EGFR signaling pathway remains unknown. The aim of this study was to investigate the effector mechanisms of FAK in the process of EGF-induced EMT in colorectal cancer cells and to determine whether miR-217 is involved in this process. Caco-2 cancer cells were routinely cultured with and without treatment with 100 ng/mL EGF, and changes in cell morphology were observed using an inverted microscope. In addition, a transwell assay was used to detect cell migration under the condition of EGF treatment. The expression of FAK, pFAK, E-cadherin, vimentin, and β actin was assessed by western blotting, and the expression of miR-217 was assessed using real-time PCR. We found that EGF induced EMT in colorectal cancer cells and enhanced cell migration and invasion ability. Moreover, FAK was involved in the EGF-induced EMT of colorectal cancer cells. EGF upregulated the expression of E-cadherin in colorectal cancer cells by activating FAK, and miR-217 was found to participate in EGF-induced EMT in colorectal cancer cells. Our findings indicate that EGF induces EMT in colorectal cancer cells by activating FAK, and miR-217 is involved in the EGF/FAK/E-cadherin signaling pathway.
Cost-Effectiveness Analysis of Biomarker-Guided Treatment for Metastatic Gastric Cancer in the Second-Line Setting
Background. The 5-year survival rate of patients with metastatic gastric cancer (GC) is only 5%. However, trials have demonstrated promising antitumor activity for targeted therapies/immunotherapies among chemorefractory metastatic GC patients. Pembrolizumab has shown particular efficacy among patients with programmed death ligand-1 (PD-L1) expression and high microsatellite instability (MSI-H). The aim of this study was to assess the effectiveness and cost-effectiveness of biomarker-guided second-line GC treatment. Methods. We constructed a Markov decision-analytic model using clinical trial data. Our model compared pembrolizumab monotherapy and ramucirumab/paclitaxel combination therapy for all patients and pembrolizumab for patients based on MSI status or PD-L1 expression. Paclitaxel monotherapy and best supportive care for all patients were additional comparators. Costs of drugs, treatment administration, follow-up, and management of adverse events were estimated from a US payer perspective. The primary outcomes were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100,000/QALY over 60 months. Secondary outcomes were unadjusted life years (survival) and costs. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. Results. The most effective strategy was pembrolizumab for MSI-H patients and ramucirumab/paclitaxel for all other patients, adding 3.8 months or 2.0 quality-adjusted months compared to paclitaxel. However, this strategy resulted in a prohibitively high ICER of $1,074,620/QALY. The only cost-effective strategy was paclitaxel monotherapy for all patients, with an ICER of $53,705/QALY. Conclusion. Biomarker-based treatments with targeted therapies/immunotherapies for second-line metastatic GC patients substantially improve unadjusted and quality-adjusted survival but are not cost-effective at current drug prices.
AXL as a Target in Breast Cancer Therapy
AXL is a receptor tyrosine kinase (RTK) that has been implicated in diverse tumor-promoting processes such as proliferation, migration, invasion, survival, and apoptosis. AXL therefore plays a role in cancer progression, and AXL has been implicated in a wide variety of malignancies from solid tumors to hematopoietic cancers where it is often associated with poor prognosis. In cancer, AXL has been shown to promote epithelial to mesenchymal transition (EMT), metastasis formation, drug resistance, and a role for AXL in modulation of the tumor microenvironment and immune response has been identified. In light of these activities multiple AXL inhibitors have been developed, and several of these have entered clinical trials in the U.S. In breast cancer, high levels of AXL expression have been observed. The role of AXL in cancer with a focus on therapeutic implications for breast cancer is discussed.
Role of 17β-Estradiol on Cell Proliferation and Mitochondrial Fitness in Glioblastoma Cells
Gliomas are the most common primary tumors of the central nervous system (CNS) in the adult. Previous data showed that estrogen affects cancer cells, but its effect is cell-type-dependent and controversial. The present study aimed to analyze the effects of estradiol (E2, 5 nM) in human glioblastoma multiforme U87-MG cells and how it may impact on cell proliferation and mitochondrial fitness. We monitored cell proliferation by xCELLigence technology and mitochondrial fitness by assessing the expression of genes involved in mitochondrial biogenesis (PGC1α, SIRT1, and TFAM), oxidative phosphorylation (ND4, Cytb, COX-II, COX IV, NDUFA6, and ATP synthase), and dynamics (OPA1, MNF2, MNF1, and FIS1). Finally, we evaluated Nrf2 nuclear translocation by immunocytochemical analysis. Our results showed that E2 resulted in a significant increase in cell proliferation, with a significant increase in the expression of genes involved in various mechanisms of mitochondrial fitness. Finally, E2 treatment resulted in a significant increase of Nrf2 nuclear translocation with a significant increase in the expression of one of its target genes (i.e., heme oxygenase-1). Our results suggest that E2 promotes proliferation in glioblastoma cells and regulate the expression of genes involved in mitochondrial fitness and chemoresistance pathway.
Identification of a Modified HOXB9 mRNA in Breast Cancer
First identified as a developmental gene, HOXB9 is also known to be involved in tumor biological processes, and its aberrant expression correlates with poor prognosis of various cancers. In this study, we isolated a homeodomain-less, novel HOXB9 variant (HOXB9v) from human breast cancer cell line-derived mRNA. We confirmed that the novel variant was produced from variationless HOXB9 genomic DNA. RT-PCR of mRNA isolated from clinical samples and reanalysis of publicly available RNA-seq data proved that the new transcript is frequently expressed in human breast cancer. Exogenous HOXB9v expression significantly enhanced the proliferation of breast cancer cells, and gene ontology analysis indicated that apoptotic signaling was suppressed in these cells. Considering that HOXB9v lacks key domains of homeobox proteins, its behavior could be completely different from that of the previously described variationless HOXB9. Because none of the previous studies on HOXB9 have considered the presence of HOXB9v, further research analyzing the two transcripts individually is warranted to re-evaluate the true role of HOXB9 in cancer.
Clinical and Survival Impact of Sex-Determining Region Y-Box 2 in Colorectal Cancer: An Integrated Analysis of the Immunohistochemical Study and Bioinformatics Analysis
Transcription factor sex-determining region Y-box 2 (SOX2) involves in the maintenance of cancer stem cells. However, the role of SOX2 in colorectal cancer (CRC) remains unclear. This study was conducted to investigate the effect of SOX2 on CRC. Studies were searched using electronic databases. The combined odds ratios (ORs) or hazard ratios (HRs: multivariate Cox survival analysis) with their 95% confidence intervals (CIs) were calculated. The Cancer Genome Atlas (TCGA) and GEO datasets were further applied to validate the survival effect. The functional analysis of SOX2 was investigated. In this work, 13 studies including 2337 patients were identified, and validation data were enrolled from TCGA and GEO datasets. SOX2 expression was not significantly related to age, gender, microsatellite instability (MSI) status, clinical stage, histological grade, tumor size, pT-stage, lymph node metastasis, distal metastasis, and cancer-specific survival (CSS) but was correlated with worse overall survival (OS: n = 536 patients) (). Furthermore, TCGA data demonstrated similar results, with no significant correlation between SOX2 and pathological characteristics. Further validation data (OS: n = 1408 and disease-free survival (DFS): n = 1367) showed that SOX2 expression was correlated with worse OS (HR = 1.35, 95% CI: 1.11–1.65, ) and DFS (HR = 1.30, 95% CI: 1.04–1.62, ). The functional analyses showed that SOX2 involved in cell-cell junction, focal adhesion, extracellular matrix- (ECM-) receptor interaction, and MAP kinase activity. Our findings suggest that SOX2 expression may be correlated with the worse prognosis of CRC.