Yang EJ, et al. J Gynecol Oncol. 2024 Mar;35:e75. https://doi.org/10.3802/jgo.2024.35.e75

OBJECTIVES: Smoking is a risk factor for gastric cancer. Studies have shown that the risk of gastric cancer can vary by smoking status and smoking amount at a single point in time. However, few data have been reported about the effect of changes in smoking status over time on the risk of gastric cancer.METHODS: This study collected data from the National Health Insurance Corporation in Korea on 97,700 Korean men without gastric cancer who underwent health check-ups from 2002 to 2013. The smoking status (never smoked, quit smoking, and currently smoking) of study participants was assessed in 2003-2004 and 2009, and the results were categorized into 7 groups: never-never, never-quit, never-current, quit-quit, quit-current, current-quit, and current-current. Participants were followed until 2013 to identify incident gastric cancer. A multivariate Cox proportional hazard model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident gastric cancer according to changes in smoking status and smoking amount (pack-years).RESULTS: Compared with group 1 (never-never), participants currently smoking in 2009 (never-current, quit-current, and current-current) had higher HRs for gastric cancer (never-quit: 1.077; 95% CI, 0.887 to 1.306, never-current: 1.347; 95% CI, 0.983 to1.846, quit-quit: 1.086; 95% CI, 0.863 to 1.366, quit-current: 1.538; 95% CI, 1.042 to 2.269, current-quit: 1.339; 95% CI, 1.077 to 1.666, and current-current: 1.589; 95% CI, 1.355 to 1.864, respectively). The risk for gastric cancer was highest in heavy smokers, followed by moderate smokers.CONCLUSIONS: In all categories of smoking status, current smoking was associated with the highest risk of gastric cancer. Heavy smoking was associated with an increased risk of gastric cancer, even in former smokers.

Background: This study aims to evaluate the incidence of and identify risk factors for gastrointestinal (GI) and genitourinary (GU) fistula or perforation formation with or without bevacizumab in patients with recurrent cervical cancer who underwent pelvic radiation therapy (RT). Methods: Medical records of patients with recurrent cervical cancer who previously underwent pelvic RT between 2007 and 2020 were retrospectively reviewed. Clinicopathological factors were compared between groups that are stratified according to: 1) fistula/perforation (+) versus (-); and 2) bevacizumab plus conventional chemotherapy (BC) versus chemotherapy alone (C). Univariate and multivariate regression analyses were performed to identify risk factors for fistula/perforation. Overall survival (OS) was compared between the different groups. Results: Of 219 participants, fistula/perforation of any grade occurred in 36 patients (16.4%); 27 fistulas and 9 perforations. Bevacizumab was more frequently used in Bevacizumab was more frequently used ( +) group than fistula/perforation (-) group (p = 0.015). Multivariate analysis showed that bevacizumab administration was the only independent risk factor for fistula or perforation (HR, 3.27; 95% CI, 1.18–9.10; P = 0.023). F/P was observed more frequently in women receiving BC (n = 144) than those receiving C (n = 75) (20.8% vs. 8.0%; P = 0.019). During median follow-up of 33.7 months (1.2–185.6 months), no significant OS difference was observed between fistula/perforation ( +) vs. (-) (hazards ratio [HR], 1.78; median 84.2 months [95% CI, 59.3–109.0] vs. 129.5 months [95% CI, 114.1–144.9]; P = 0.065) or BC vs. C (HR, 1.03; median 119.8 months [95% CI, 97.3–142.3] vs. 115.7 months [95% CI, 96.0–135.4]; P = 0.928). Conclusions: This study suggests that incorporation of bevacizumab in chemotherapy regimens for treating recurrent cervical cancer in patients who underwent pelvic RT incurs considerable risk for GI/GU fistula or perforation. There were no other independent risk factors for developing GI/GU fistula or perforation in this study population.

Cold atmospheric plasma (CAP) has rapidly advanced as a pivotal area in medical research, notably in wound healing and cancer therapy. This review presents an overview of the mechanisms underlying the action of CAP on wound healing and cancer treatment. CAP plays opposing roles in wound healing and cancer treatment. In wound healing, CAP promotes cell migration and proliferation and eradicates pathogens near the wound site. In cancer therapy, CAP has been recognized for its ability to induce cell death through multiple mechanisms. These include activating the mitochondrial pathway, provoking endoplasmic reticulum stress, generating reactive oxygen species (ROS) and reactive nitrogen species (RNS), causing DNA damage, arresting the cell cycle, and modulating signaling pathways. Additionally, CAP’s oxidative stress can lead to significant changes in DNA and RNA within the nucleus, further contributing to its anti-cancer properties. These diverse effects underscore CAP’s therapeutic potential, though outcomes may differ based on the type of cancer and experimental settings. Furthermore, we compared the CAP application conditions for wound healing and cancer cell treatment. The type and concentration of ROS and RNS depend on plasma generation and treatment conditions. Thus, we aimed to identify the correlations between plasma properties and mechanisms of action by comparing CAP generation and treatment conditions in wound healing and cancer cell treatment.

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.

Objectives: The objective is to evaluate the prognostic value of serum human epididymis protein 4 (HE4) as a tumor marker in patients with cervical cancer. Methods: Sixty-seven patients with cervical cancer treated at Seoul National University Bundang Hospital from September 2014 to May 2018 were retrospectively reviewed. Serum HE4 levels were measured by immunoassay before starting primary treatment. A mean serum HE4 level of 72.6 pmol/L was used to divide the patients into low and high HE4 groups. Patient characteristics, clinicopathological variables, and survival outcomes were compared between the two groups. Results: The low and high HE4 groups included 55 (82.1%) and 12 (17.9%) patients at diagnosis, respectively. Higher HE4 levels were significantly associated with older age at diagnosis (age <50: .0% vs age ≥50: 100.0%; P = .002), menopause (premenopause: 8.3% vs postmenopause: 91.7%; P = .009), higher FIGO stage (stage I–II: 33.3% vs III–IV: 66.7%; P = .017), large tumor size (<4.0 cm: 41.7% vs ≥4.0 cm: 58.3%; P = .029), positive lymph node metastasis (negative: 41.7% vs positive: 58.3%; P = .049), and involvement of the parametrium (negative: 25.0% vs positive: 75.0%; P = .002). Higher HE4 level was a predictive factor for worse overall survival but not for progression-free survival. Elevated HE4 levels were not independent factors for the prediction of either overall survival or progression-free survival. Subgroup analysis by histological type revealed similar results for patients with squamous cell carcinoma. Conclusions: High levels of HE4 expression correlated with poor overall survival, indicating that elevated HE4 levels are associated with a poor prognosis for patients with cervical cancer.