Journal of Investigative Medicine

Bruceine D and afatinib combination inhibits ovarian cancer cells proliferation and migration through DNA damage repair and EGFR pathway

Owing to the high rates of relapse and migration, ovarian cancer (OC) has been recognized as the most lethal gynecological malignancy worldwide. The activity of the epidermal growth factor receptor (EGFR) signaling pathway is frequently associated with OC cell proliferation and migration. Despite this knowledge, inhibition of EGFR signaling in OC patients failed to achieve satisfactory therapeutic effects. In this study, we identified that bruceine D (BD) and EGFR inhibitor, afatinib, combination resulted in synergistic anti-OC effects. The results indicated that compared with one of both drugs alone, the combination of BD and afatinib slowed the DNA replication rate, inhibition of cell viability, and proliferation and clone formation. This resulted in cell cycle arrest and cell apoptosis. In addition, the combination of BD and afatinib possessed a stronger ability to inhibit the OC cell adhesion and migration than treatment with BD or afatinib alone. Mechanistically, the combined treatment triggered intense DNA damage, suppressed DNA damage repair, and enhanced the inhibition of the EGFR pathway. These results demonstrated that compared with each pathway inhibition, combined blocking of both DNA damage repair and the EGFR pathway appears to more effective against OC treatment. The results support the potential of BD and afatinib combination as a therapeutic strategy for OC patients.

Prostate cancer screening: Is it time for a new approach? A review article

Prostate cancer screening has presented a challenge to clinicians. Although the implementation of screening tests such as prostate-specific antigen (PSA) and digital rectal exam (DRE) has had a significant impact on prostate-cancer-specific mortality, these traditional screening tests have a relatively poor positive predictive value of clinically significant prostate cancer (CSPC), leading to unnecessary biopsies and treatment with a host of potential complications. Fortunately, much research has been done to optimize prostate cancer screening. This includes the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which underwent a secondary analysis to identify an association between PSA level and CSPC, and the IP1-PROSTAGRAM Tri

Utility of serum NAMPT concentrations in clinical management of HPV-infected patients

The expression of nicotinamide-phosphoribosyl transferase (NAMPT) was demonstrated to increase in various dysplastic and malignant conditions, usually consistent with the severity of the disease. This study was conducted to assess the utility of extracellular NAMPT (eNAMPT) in the management of cervical dysplasia in human papillomavirus (HPV) infected women. Circulating eNAMPT concentrations in high-risk HPV-infected women who were diagnosed with high-grade squamous intraepithelial lesion (HSIL) or invasive cancer (cervical intraepithelial neoplasia 2+ (CIN2+) lesions) and who were revealed to have no cervical dysplasia or low-grade squamous intraepithelial lesion (LSIL) were evaluated and compared. One hundred fifty nine high-risk HPV-infected patients for cervical biopsies under colposcopy guidance between February 2022 and February 2023 were included in this case–control study. Study group composed of consecutively enrolled 84 women with histological diagnosis of HSIL or cervical cancer (CIN2+ lesions) and control group composed of consecutively enrolled 75 women with LSIL or normal cervical biopsies. Circulating eNAMPT concentrations of cases with CIN2+ lesions and cases with LSIL or normal cervical biopsies were compared. No significant difference was found between median peripheral venous blood eNAMPT concentration of cases with histologic diagnosis of CIN2+ lesions and cases with LSIL or normal cervical biopsies (9.4 ng/mL (0.19–192) vs 8.9 ng/mL (0.19–176.9); p = 0.07, respectively). Multivariate linear regression analysis revealed no independent predictor of circulating eNAMPT concentrations among possible predictor variables. In conclusion, circulating eNAMPT concentrations of cases with CIN2+ lesions and cases with LSIL or normal cervical biopsies were found to be similar. Further research that evaluates cervical fluid eNAMPT concentrations might define novel noninvasive tools in cervical dysplasia management.

Analysis of Count Data in the Setting of Cervical Cancer Detection

Women with an abnormal Pap smear are often referred to colposcopy, a procedure during which endocervical curettage (ECC) may be performed. ECC is a scraping of the endocervical canal lining. Our goal was to compare the performance of a naïve Poisson (NP) regression model with that of a zero-inflated Poisson (ZIP) model when identifying predictors of the number of distress/pain vocalizations made by women undergoing ECC. Data on women seen in the colposcopy clinic at a medical school in El Paso, Texas, were analyzed. The outcome was the number of pain vocalizations made by the patient during ECC. Six dichotomous predictors were evaluated. Initially, NP regression was used to model the data. A high proportion of patients did not make any vocalizations, and hence a ZIP model was also fit and relative rates (RRs) and 95% CIs were calculated. AIC was used to identify the best model (NP or ZIP). Of the 210 women, 154 (73.3%) had a value of 0 for the number of ECC vocalizations. NP identified three statistically significant predictors (language preference of the subject, sexual abuse history and length of the colposcopy), while ZIP identified one: history of sexual abuse (yes vs no; adjusted RR=2.70, 95% CI 1.47 to 4.97). ZIP was preferred over NP. ZIP performed better than NP regression. Clinicians and epidemiologists should consider using the ZIP model (or the zero-inflated negative binomial model) for zero-inflated count data.

Advanced Clinical Trials of Dendritic Cell Vaccines in Ovarian Cancer

Epithelial ovarian cancer (EOC) is the most common and leading cause of death for gynecologic cancer in the western world. Current standard treatments with limited selection of chemotherapies cannot meet patients’ urgent needs. Immunotherapies have recently demonstrated clinical benefits in a variety of solid tumors and may offer a promising frontier for treating EOC. Dendritic cells (DCs) are key coordinators of the innate and adaptive immune system in induction of antitumor immunity. DC-based vaccinations showed clinical benefits and encouraging safety profiles in a few phase II clinical trials for patients with EOC and currently are in a phase III double-blind, randomized, placebo-controlled clinical trial. In this review, we have searched Pubmed and Clinicaltrials. gov databases for past and current phase II or phase III clinical trials with focus on EOC and DC vaccines. Outcomes and implications of the completed and ongoing trials are discussed.

Circular Rna Hipk3 Plays a Carcinogenic Role in Cervical Cancer Progression via Regulating Mir-485-3P/Fgf2 Axis

Circular RNA (circRNA) is an endogenous RNA molecule with a stable closed-loop structure. The circular RNA HIPK3 (circHIPK3) is highly expressed in hepatocellular carcinoma and facilitates tumor growth. However, its role in cervical cancer (CC) and its regulatory mechanisms are not well-studied. This study aimed for investigating the function of circHIPK3 on proliferation and metastasis of CC cells. In this study, quantitative real-time PCR assay was adopted to delve into the circHIPK3 expression in CC cell lines. Cell counting kit-8 and colony formation assays were used to evaluate the influence of overexpression and knockdown of circHIPK3 on CC cell proliferation. Dual-luciferase reporter assay was employed to probe into the binding of miR-485-3p to circHIPK3 and miR-485-3p to the 3’ untranslated region (UTR) of fibroblast growth factor 2 (FGF2), respectively. FGF2 protein expression was detected by western blot analysis. This study confirmed that circHIPK3 was highly expressed in CC tissues. Overexpressed circHIPK3 could remarkably expedite the proliferation, migration and invasion of SiHa cells, and knocking down circHIPK3 could significantly impede the proliferation, migration and invasion of HeLa cells. MiR-485-3p can directly bind to circHIPK3 and the 3'UTR of FGF2. Overexpression of circHIPK3 triggered the upregulation of FGF2 expression while knockdown of circHIPK3 reduced FGF2 expression in CC cells, and the transfection of miR-485-3p mimics reversed the upregulation of FGF2 expression and enhanced malignant phenotypes in CC cells with overexpressed circHIPK3.

RETRACTED: Mir-3150B-3P Inhibits the Proliferation and Invasion of Cervical Cancer Cells by Targeting Tnfrsf11A

The objective of this study was to determine the role of miR-3150b-3p in the cervical cancer (CC) progression. Real-time PCR and western blot analysis were conducted to test the expression of miR-3150b-3p, TNFRSF11a and p38 mitogen-activated protein kinase (MAPK) signaling pathway. The interaction between miR-3150b-3p and TNFRSF11a was verified by luciferase assay. Cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. In this study, we showed that miR-3150b-3p was significantly downregulated in CC cell lines. Additionally, miR-3150b-3p markedly attenuated the proliferation, migration and invasion of HeLa and SiHa cells. Moreover, we identified TNFRSF11a to be a novel target of miR-3150b-3p in CC cells. Enforced expression of TNFRSF11a abolished the antitumor effect of miR-3150b-3p. Besides, miR-3150b-3p was involved in the regulation of the p38 MAPK signaling pathway. In conclusion, our data suggested that miR-3150b-3p directly targets TNFRSF11a to inactivate the p38 MAPK signaling pathway, thus implicating miR-3150b-3p in the regulation of CC cell growth.