World Journal of Oncology最新文献

Background: The aim of the study was to assess the effect of multicentricity on the recurrence/persistence of high-grade vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VAIN) after laser vaporization.

Methods: A retrospective cohort study was conducted on patients diagnosed with high-grade VIN/VAIN, who had undergone laser vaporization between 1997 and 2014. Recurrence/persistence rates and factors affecting recurrence/persistence were analyzed, and a life table analysis of recurrence-free intervals was conducted.

Results: Among the 65 patients, the recurrence/persistence rate following laser vaporization was 22.3 per 100 person-years, with a median time to recurrence/persistence of 31.2 months (95% confidence interval (CI): 0.0 - 71.9 months). Patients with multicentricity and unicentricity had a recurrence/persistence rate of 49.1 per 100 person-years, with a median time to recurrence/persistence of 11.4 months, and 7.4 per 100 person-years, with a median time to recurrence/persistence of 96.5 months, respectively (P = 0.0002). The difference in recurrence-free survival between the multicentricity and unicentricity groups was significant (P = 0.00035). Patients with multicentricity had a 4.7-fold higher risk of recurrence/persistence (hazard ratio (HR): 4.71, 95% CI: 1.87 - 11.88, P = 0.001). Multivariate analysis showed that multicentricity was an independent risk factor for recurrence/persistence (odds ratio (OR): 4.16, 95% CI: 1.56 - 11.06, P = 0.004).

Conclusions: Treatment of multicentric, high-grade VIN/VAIN with laser vaporization is strongly associated with treatment failure, with approximately half of patients experiencing recurrence/persistence.

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignant tumor of the biliary tract that is prone to recurrence and metastasis and is characterized by poor sensitivity to chemotherapy and overall prognosis. For these reasons, there is an urgent need to understand its pathological mechanisms and develop effective treatments. To address this challenge, the establishment of suitable preclinical models is critical.

Methods: Fresh ICC tissue samples were used for primary culture and subculture. The cell line was evaluated by cell proliferation assays, clonal formation assays, karyotype analysis, and short tandem repeat (STR) analysis. Drug resistances against oxaliplatin, paclitaxel, gemcitabine and 5-fluorouracil (5-FU) were evaluated by CCK-8 assay. Subcutaneous injection of 1 × 10⁶ cells to three BALB/c nude mice was conducted for xenograft studies. The hematoxylin and eosin (H&E) staining was used to detect the pathological status of the cell line. The expression of biomarkers CK7, CK19, Ki-67, E-cadherin and vimentin was determined by immunocytochemistry assay.

Results: A new ICC cell line named ICC-X2 was successfully established. Like ICC-X3 established using the same patient's metastatic tumor, the cell line has been continuously cultured in vitro for more than a year and has been passaged more than 100 times. ICC-X2 retained the typical biliary epithelial morphology. The population doubling time of ICC-X2 is 48 h. The cells demonstrated an abnormal nearly tetraploid karyotype. The STR analysis confirmed that ICC-X2 was highly consistent with the primary tumor tissue and not cross-contaminated by existing cell lines. ICC-X2 cells positively expressed CK7, CK19, E-cadherin, and vimentin, and the positive expression of Ki-67 in ICC-X2 cells was 40%. The ICC-X2 cells exhibited a strong clonogenic ability. The drug sensitivity test indicated that ICC-X2 was sensitive to oxaliplatin and paclitaxel, but naturally resistant to gemcitabine and 5-FU. ICC-X2 was rapidly able to form transplanted tumors in vivo after subcutaneous inoculation in nude mice.

Conclusions: ICC-X2 is an excellent experimental model that can be used for studying the occurrence, development, and metastasis of ICC and investigating the mechanism of tumor drug resistance.

Overcoming and preventing cancer therapy resistance is the most pressing challenge in modern breast cancer management. Consequently, most modern breast cancer research is aimed at understanding and blocking these therapy resistance mechanisms. One increasingly promising therapeutic target is the autotaxin (ATX)-lysophosphatidate (LPA)-lipid phosphate phosphatase (LPP) axis. Extracellular LPA, produced from albumin-bound lysophosphatidylcholine by ATX and degraded by the ecto-activity of the LPPs, is a potent cell-signaling mediator of tumor growth, invasion, angiogenesis, immune evasion, and resistance to cancer treatment modalities. LPA signaling in the post-natal organism has central roles in physiological wound healing, but these mechanisms are subverted to fuel pathogenesis in diseases that arise from chronic inflammatory processes, including cancer. Over the last 10 years, our understanding of the role of LPA signaling in the breast tumor microenvironment has begun to mature. Tumor-promoting inflammation in breast cancer leads to increased ATX production within the tumor microenvironment. This results in increased local concentrations of LPA that are maintained in part by decreased overall cancer cell LPP expression that would otherwise more rapidly break it down. LPA signaling through six G-protein-coupled LPA receptors expressed by cancer cells can then activate virtually every known tumorigenic pathway. Consequently, to target therapy resistance and tumor growth mediated by LPA signaling, multiple inhibitors against the LPA signaling axis are entering clinical trials. In this review, we summarize recent developments in LPA breast cancer biology, and illustrate how these novel therapeutics against the LPA signaling pathway may be excellent adjuncts to extend the efficacy of evolving breast cancer treatments.

The dynamic changes between glycolysis and oxidative phosphorylation (OXPHOS) for adenosine triphosphate (ATP) output, along with glucose, glutamine, and fatty acid utilization, etc., lead to the maintenance and selection of growth advantageous to tumor cell subgroups in an environment of iron starvation and hypoxia. Iron plays an important role in the three major biochemical reactions in nature: photosynthesis, nitrogen fixation, and oxidative respiration, which all require the participation of iron-sulfur proteins, such as ferredoxin, cytochrome b, and the complex I, II, III in the electron transport chain, respectively. Abnormal iron-sulfur cluster synthesis process or hypoxia will directly affect the function of mitochondrial electron transfer and mitochondrial OXPHOS. More research results have indicated that iron metabolism, oxygen availability and hypoxia-inducible factor mutually regulate the shift between glycolysis and OXPHOS. In this article, we make a perspective review to provide novel opinions of the regulation of glycolysis and OXPHOS in tumor cells.

Background: Ovarian cancer is an extremely deadly gynecological malignancy, with a 5-year survival rate below 30%. Among the different histological subtypes, serous ovarian cancer (SOC) is the most common. Anoikis significantly contributes to the progression of ovarian cancer. Therefore, identifying an anoikis-related signature that can serve as potential prognostic predictors for SOC is of great significance.

Methods: We intersected 308 anoikis-related genes (ARGs) and identified those significantly associated with SOC prognosis using univariate Cox regression. A LASSO Cox regression model was constructed and evaluated using Kaplan-Meier and receiver operating characteristic (ROC) analyses in TCGA (The Cancer Genome Atlas) and GSE26193 cohorts. We conducted quantitative real-time polymerase chain reaction (qPCR) to assess mRNA levels and applied bioinformatics to investigate the correlation between risk groups and gene expression, mutations, pathways, tumor immune microenvironment (TIME), and drug sensitivity in SOC.

Results: Among 308 ARGs, 28 were significantly associated with SOC prognosis. A 13-gene prognostic model was established through LASSO Cox regression in TCGA cohort. High-risk group had poorer prognosis than low-risk group (median overall survival (mOS): 34.2 vs. 57.1 months, hazard ratio (HR): 2.590, 95% confidence interval (CI): 0.159 - 6.00, P < 0.001). The area under the curve (AUC) values of 0.63, 0.65, and 0.74 reflected the predictive performance for 3-, 5-, and 8-year overall survival (OS) in GSE26193 validation cohort. Functional enrichment, pathway analysis, and TIME analysis identified distinct characteristics between risk groups. Drug sensitivity analysis revealed potential drug advantages for each group. Furthermore, qPCR validation once again confirmed the effectiveness of the risk model in SOC patients.

Conclusions: We developed and validated a robust ARG model, which could be used to predict OS in SOC patients. By systematically analyzing the correlation between the risk score of the ARGs signature model and various patterns, including the TIME and drug sensitivity, our findings suggest that this prognostic model contributes to the advancement of personalized and precise therapeutic strategies. Nevertheless, further validation studies and investigations into the underlying mechanisms are warranted.

Background: Non-small cell lung cancer (NSCLC) stands as one of the most prevalent types of cancer worldwide, driving extensive research in oncologic therapeutic approaches. Atezolizumab, among the treatments under scrutiny, is undergoing evaluation as a potential first-line therapy for NSCLC. This review aims to assess the efficacy of atezolizumab in treating patients with NSCLC and to shed light on the ongoing quest for the most effective treatment.

Methods: Multiple scientific databases, including PubMed, Cochrane, and ScienceDirect, were consulted. The literature identification utilized the strategic Boolean term method of keywords relating to "non-small cell lung cancer" and "atezolizumab" to suggest the analyzed population in our review without restricting the potential outcomes. The primary inclusion criterion is clinical studies that attempted to determine the efficacy of atezolizumab in NSCLC patients.

Results: We included four trials to be analyzed in the final analysis, which we stratified into the programmed cell death-ligand 1 (PD-L1) expressivity status aside from the pooled intention-to-treat (ITT) population. We found the addition of atezolizumab may significantly improve the overall survival (OS) in the respective arm, remarkably among the high PD-L1 expression group (TC3 or IC3). The result of our meta-analysis presented the pooled OS of 0.79 (0.72, 0.87) in 95% confidence interval (CI) with a P value of < 0.05. Sub-analysis of the PD-L1's expression revealed TC3 population benefits the most (hazard ratio (HR): 0.55, 95% CI (0.42, 0.73)), compared to low (HR: 0.80, 95% CI (0.68, 0.93)) and negative expression (HR: 0.79, 95% CI (0.68, 0.93)); which is statistically meaningful (P < 0.05). Similar result was also observed in progression-free survival (PFS) analysis with the HR value of 0.63 (0.55, 0.72), with P value of < 0.05, favoring atezolizumab arm.

Conclusions: Upon examination, the study reveals that the addition of atezolizumab demonstrates notable improvements in both OS and PFS among NSCLC patients. These findings present promising attributes for atezolizumab as a viable treatment for NSCLC. However, it is important to acknowledge that the future holds further revelations in this realm, and more insights are yet to be uncovered.

Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m⁶A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown.

Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition.

Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression.

Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.

Uterine leiomyosarcoma is a high-grade sarcoma that might be associated with dismal outcome. There are no hematological markers that can be used to follow up the recurrence and/or progression of the tumor. We present a case of a 44-year-old female, who was diagnosed with uterine leiomyosarcoma. During her management course, serum beta human chorionic gonadotropin (β-hCG) elevation was correlated with clinical and radiological disease progression on two separate occasions. This correlation should be further investigated to potentially integrate serum β-hCG as a predictive tool for clinical behavior and treatment response.

Background: There is no literature report on how metformin and adenosine monophosphate-activated protein kinase (AMPK) inhibitor affect normal and cancer bladder cells under the presence of nitrate.

Methods: Various treatment concentrations and methods were used to study the effects of nitrate, metformin, and/or AMPK inhibitor on normal and/or cancer bladder cells. Normal bladder cells were exposed to nitrate or metformin alone or in combination. The effects of AMPK on normal bladder cells were investigated with nitrate and metformin pretreatment. The effects of varying metformin concentrations on cancer bladder cells were examined as well.

Results: Metformin has produced almost no changes in cell viability of normal cells with various concentrations. Addition of both nitrate and metformin at the same time resulted in less than 17% cell viability as compared to the controlled values; however, this value is about 10% better than nitrate alone for 24 h and approximate 27% better for 48 h. Pre-treatment of normal cells with AMPK inhibitor for 6 h prior to addition of metformin and nitrate reduced the cell viability greatly. The treatment of cancer bladder cells with metformin indicated an inverse relationship between metformin concentration and cancer bladder cell viability.

Conclusion: Metformin assisted normal bladder cells in surviving in the presence of nitrate, but its total survival was greatly reduced by AMPK inhibitors. Metformin inhibited the growth of bladder cancer cells.