Efficacy of immune-checkpoint inhibitors combined with cytotoxic chemotherapy in advanced or recurrent endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. METHODS: We conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). FINDINGS: Four trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62-0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63-0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26-0.43; OS; HR, 0.37; 95% CI, 0.22-0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54-0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56-0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19-0.81) over PD-L1 negative population. INTERPRETATION: ICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes.

Mapping recommendations towards an Asian Code Against Cancer (ACAC) as part of the World Code Against Cancer Framework: an Asian National Cancer Centers Alliance (ANCCA) initiative.

This paper outlines the process undertaken by Asian National Cancer Centers Alliance (ANCCA) members in working towards an Asian Code Against Cancer (ACAC). The process involves: (i) identification of the criteria for selecting the existing set of national recommendations for ACAC (ii) compilation of existing national codes or recommendations on cancer prevention (iii) reviewing the scientific evidence on cancer risk factors in Asia and (iv) establishment of one or more ACAC under the World Code Against Cancer Framework. A matrix of national codes or key recommendations against cancer in ANCCA member countries is presented. These include taking actions to prevent or control tobacco consumption, obesity, unhealthy diet, physical inactivity, alcohol consumption, exposure to occupational and environmental toxins; and to promote breastfeeding, vaccination against infectious agents and cancer screening. ANCCA will continue to serve as a supportive platform for collaboration, development, and advocacy of an ACAC jointly with the International Agency for Research on Cancer/World Health Organization (IARC/WHO).

Suicide mortality following the implementation of tobacco packaging and pricing policies in Korea: an interrupted time-series analysis.

BACKGROUND: To prevent tobacco use in Korea, the national quitline number was added to tobacco packages in December 2012, tobacco prices were raised by 80% in January 2015, and graphic health warning labels were placed on tobacco packages in December 2016. This study evaluated the association of these tobacco packaging and pricing policies with suicide mortality in Korea. METHODS: Monthly mortality from suicide was obtained from Cause-of-Death Statistics in Korea from December 2007 to December 2019. Interrupted time-series analysis was performed using segmented Poisson regression models. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated adjusted for suicide prevention strategies. RESULTS: Suicide mortality was 20 per 1,000,000 in December 2007 and showed a downward trend over the study period. After the implementation of tobacco packaging and pricing policies, suicide mortality immediately declined by - 0.09 percent points (95% CI = - 0.19 to 0.01; P > 0.05) for the national quitline number, - 0.22 percent points (95% CI = - 0.35 to - 0.09; P < 0.01) for tobacco prices, and - 0.30 percent points (95% CI = - 0.49 to - 0.11; P < 0.01) for graphic health warning labels. The corresponding RRs for these post-implementation changes compared with the pre-implementation level were 0.91 (95% CI = 0.83 to 1.00), 0.80 (95% CI = 0.70 to 0.91), and 0.74 (95% CI = 0.61 to 0.90), respectively. Significant associations between tobacco control policies and suicide mortality were observed even when stratified by sex and region. CONCLUSIONS: The findings of this study provide new evidence for an association between tobacco control policies and deaths by suicide. An array of effective tobacco control policies should be considered for prevention programs targeting suicide.

Preparation of catechin-starch nanoparticles composites and its application as a Pickering emulsion stabilizer.

Starch is a biopolymer commonly used for nanoparticle synthesis. Starch nanoparticles (SNPs) have potential as encapsulation agents and Pickering emulsion stabilizers. Here, we prepared SNPs by dry heating under mildly acidic conditions to encapsulate catechin. Catechin (30 mg) and SNPs (50-150 mg) were dispersed in distilled water and freeze-dried to prepare catechin-SNP composites. Isothermal titration calorimetry and Fourier-transform infrared spectroscopy revealed that the binding of catechin to SNP may involve spontaneous hydrogen bonding and hydrophobic interactions. SNPs exhibited encapsulation efficiency for catechin, with 100 % catechin retention when 150 mg of SNP was used to prepare the composites. The catechin-SNP composites had a particle size of 54.2-74.9 nm. X-ray diffraction analysis revealed the formation of small amounts of inclusion complexes in catechin-SNP composites. As the amount of SNPs added for encapsulation increased, the catechin encapsulated in the SNP composites exhibited higher water solubility and UV stability than the pure catechin. The catechin-SNP composite with 150 mg of catechin exhibited the highest contact angle (51.37°) and formed a stable emulsion without notable droplet size changes. Therefore, catechin-SNP composites improved the encapsulation efficiency, water-solubility, stability of catechins, and Pickering emulsion stability.

Disseminating Necrotizing Leukoencephalopathy Associated With Intra-CSF Methotrexate Chemotherapy: A Retrospective Observational Study.

BACKGROUND AND OBJECTIVES: Leptomeningeal metastases (LMs) are neoplasms that proliferate to membranes lining the brain and spinal cord. Intra-CSF methotrexate (MTX) chemotherapy is a prevalent treatment option. However, resultant long-term neurotoxicity can lead to irreversible disseminated necrotizing leukoencephalopathy (DNL). This study aims to determine the incidence, characteristics, risk factors, and outcomes of DNL following intra-CSF MTX chemotherapy for LM. METHODS: We retrospectively reviewed patients with LM who received intra-CSF MTX between 2001 and 2021 at the National Cancer Center of Korea. Patients with a follow-up duration of <3 months and those without follow-up MRI after MTX administration were excluded. The primary outcome was the development of DNL, evaluated based on the clinical and radiologic definitions of DNL. Logistic and Cox proportional regression models were used to assess the risk of DNL in patients with LM receiving intra-CSF MTX chemotherapy. RESULTS: Of the 577 patients included in the DNL investigation, 13 (2.3%) were identified to have irreversible DNL. The MRI features of DNL typically include necrotic changes in the bilateral anterior temporal region, extensive white matter, and/or brainstem lesions. All patients with DNL experienced fatal clinical course despite MTX cessation. Logistic regression analysis revealed that a cumulative dose of MTX significantly affected DNL occurrence. Multivariable analysis showed that the factor of ≥10 MTX rounds was significant for DNL development after adjusting for route of MTX administration and prior brain radiotherapy (odds ratio 7.32, 95% CI 1.42-37.77 at MTX rounds ≥10 vs < 10). In the Cox proportional hazards model considering time to occurrence of DNL, ≥10 rounds of MTX were identified as an independent predictor of DNL (hazard ratio 12.57, 95% CI 1.62-97.28, p = 0.015), even after adjusting for the synergistic effect of brain radiotherapy. DISCUSSION: DNL is a rare but fatal complication of intra-CSF MTX chemotherapy, and its progression cannot be prevented despite early recognition. The cumulative dose of intra-CSF MTX was an independent risk factor for DNL occurrence. Thus, intra-CSF MTX treatment for patients with LM should be administered with caution considering the possibility of the cumulative irreversible neurotoxicity.

Antiphotoaging effects of solvent fractions isolated from Allomyrina dichotoma larvae extract.

Skin aging is affected by a variety of factors, including ultraviolet rays, oxidative stress, medications, smoking, and genetics. Among them, photo-aging accounts for about 80% of skin aging. The present study was evaluated to verify the potential of Allomyrina dichotoma larvae, which has recently been attracting attention as an edible insect, as an anti-aging substance. UVB irradiation at 100 mJ/cm2 was sufficient to induce photo-aging of fibroblasts within 24 h, which was alleviated after treatment with 70% ethanol extract of Allomyrina dichotoma larvae extract (ADLE). To obtain an extract from ADLE, which has a relatively high content of polyphenol compounds containing physiological activity, fractional solvent extraction was carried out using organic solvents such as hexane, chloroform, ethyl acetate, and butanol. Additionally, ethyl acetate and butanol fractions contributed to the inhibition of UVB-induced ROS production, cell damage, and senescence of fibroblasts. It was also confirmed that the two fractions can regulate the expression of MMP-1 and AP-1. In particular, the ethyl acetate fraction showed an excellent effect in recovering collagen decomposed by UVB. Therefore, these results suggest that ADLE has potential as a natural insect-derived biomaterial to inhibit UVB-induced photo-aging.

Impact of advanced maternal age on perinatal outcomes in Tanzania: Insights from Kilimanjaro Christian Medical Center Birth Registry.

The increasing prevalence of advanced maternal age (AMA) births necessitates the exploration of associated pregnancy outcomes within the healthcare-limited context of northern Tanzania to elucidate potential region-specific risks and implications. This study explored the influence of AMA on pregnancy outcomes in northern Tanzania, where healthcare resources and infrastructure are constrained in comparison to developed countries. This cross-sectional hospital-based study utilized maternally linked data from the Kilimanjaro Christian Medical Center (KCMC) Medical Registry and included 32,798 women who delivered single infants between 2004 and 2013. Multiple logistic regression models were used to determine adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AMA-associated adverse pregnancy outcomes. A total of 16 % of mothers belonged to AMA with increased odds of undergoing a cesarean section (aOR: 1.32; 95%CI [1.24-1.41]; P < 0.001), gestational diabetes (aOR: 13.16; 95%CI [3.28-52.86]; P < 0.001) or pregestational diabetes (aOR: 3.15; 95%CI [1.87-5.31]; P < 0.000), and developing pre-eclampsia (aOR: 1.63; 95%CI [1.41-1.89]; P < 0.000). More women with AMA reported alcohol use during pregnancy and had preexisting conditions before conception than did younger women. Maternal education level, employment status, urban residency, and Christianity were statistically significant. This study establishes a connection between AMA and higher odds of cesarean section, gestational diabetes, pregestational diabetes, and pre-eclampsia. Women with AMA were more inclined to consume alcohol during pregnancy and exhibited preexisting conditions before conception. Moreover, AMA was linked to increased odds of low birth weight, stillbirths, and NICU transfers.

Environmental exposure to lead and cadmium are associated with triglyceride glucose index.

The triglyceride glucose (TyG) index was suggested as a novel reliable surrogate marker for insulin resistance and related cardiovascular-metabolic diseases. We aimed to evaluate the association between the TyG index and environmental exposure to lead (Pb), mercury (Hg), and cadmium (Cd). A total of 9645 adults who enrolled in the Korea National Health and Nutrition Examination Survey in 2005, 2008-2013, and 2016 were included. Fasting plasma glucose and triglyceride levels were used to calculate the TyG index. Multivariate logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We noted an increasing trend in the TyG index with increment of blood Pb and Cd concentrations. Participants in the highest quartile of blood Pb and Cd concentrations had higher TyG index values than those in the lowest quartile, with ORs (95% CIs) of 1.32 (1.07-1.63) and 1.29 (1.04-1.59) for Pb and Cd, respectively. Strong associations between blood Pb and Cd concentrations and the TyG index were found in men. Blood Hg concentrations did not show a significant association with the TyG index. Our study suggests that public health strategies for cardiovascular-metabolic disorder prevention should be directed toward individuals exposed to priority heavy metals.

Comparison of survival outcomes between olaparib and niraparib maintenance therapy in BRCA-mutated, newly diagnosed advanced ovarian cancer.

INTRODUCTION: This multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between maintenance therapy with two poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and niraparib, in patients with BRCA-mutated, newly diagnosed advanced epithelial ovarian cancer (EOC) who responded to platinum-based chemotherapy. METHODS: We enrolled stage III-IV EOC patients with germline and/or somatic BRCA1/2 mutations that had received maintenance therapy with olaparib or niraparib. A 3:1 propensity score matching was conducted using two variables: residual disease size and the presence of germline variants. The primary outcome was progression-free survival (PFS), and the secondary outcomes were time to first subsequent therapy (TFST), overall survival (OS), and treatment-emergent adverse events (TEAEs). RESULTS: In the propensity score-matched analysis, 80 patients who received olaparib and 31 patients who received niraparib were matched (3:1). In the propensity score-matched cohort, median PFS with olaparib vs. niraparib was not reached vs 31.5 months (HR, 1.08; 95% CI, 0.47-2.52; p = 0.854). The median TFST was not reached vs 31.8 months (HR, 1.20; 95% CI, 0.51-2.81; p = 0.682), and neither olaparib nor niraparib reached the median OS (HR, 0.42; 95% CI, 0.01-17.61; p = 0.649). In terms of the incidence rates of any-grade hematologic or non-hematologic TEAEs, higher rates of thrombocytopenia (p = 0.021) and neutropenia (p = 0.011) were observed in the niraparib group. CONCLUSION: Advanced EOC patients with BRCA1/2 mutations exhibited no significant difference in OS between olaparib and niraparib, indicating the need to consider individualized strategies for selecting PARP inhibitors based on adverse event profiles.

Effects of an urban forest healing program on cancer-related fatigue in cancer survivors.

PURPOSE: This study aimed to examine the effects of an eight-session structured urban forest healing program for cancer survivors with fatigue. BACKGROUND: Cancer-related fatigue (CRF) is a complex and multifactorial common symptom among cancer survivors that limits quality of life (QoL). Although health benefits of forest healing on physiological, physical, and psychological aspect as well as on the immune system have been reported in many studies, there is limited evidence on the efficacy of specialized forest program for cancer survivors. METHOD: A single-blinded, pre-test and post-test control group clinical trial was conducted with -75 cancer survivors assigned to either the forest healing group or the control group. The intervention was an eight-session structured urban forest program provided at two urban forests with easy accessibility. Each session consists of three or four major activities based on six forest healing elements such as landscape, phytoncides, anions, sounds, sunlight, and oxygen. Complete data of the treatment-adherent sample (≥ 6 sessions) was used to examine whether sociodemographic, clinical, physiological (respiratory function, muscle strength, balance, 6-min walking test) and psychological (distress, mood state, sleep quality, QoL) characteristics at baseline moderated the intervention effect on fatigue severity at 9 weeks. RESULTS: Significant time-group interactions were observed muscle strength, balance, 6-min walking test, distress, fatigue, moods, and QoL. The mean difference in fatigue between pre- and post-forest healing program was 9.1 (95% CI 6.2 to 11.9), 11.9 (95% CI 7.6 to 16.1) in moods, and -93.9 (95% CI -123.9 to -64.0) in QoL, showing significant improvements in forest healing group, but no significant improvements in the control group. CONCLUSION: This study suggests that a forest healing program positively impacts the lives of cancer survivors, by addressing both physical and psychological challenges associated with CRF. TRIAL REGISTRATION NUMBER: KCT0008447 (Date of registration: May 19, 2023).

Association between Proinflammatory Cytokines and Lung Cancer Risk: A Case-Cohort Study from a Community-Based Prospective Cohort.

Recent studies have shed light on alterations to the proinflammatory tumor microenvironment as a significant carcinogenic mechanism. Despite previous studies on associations between proinflammatory cytokines and lung cancer risk, few studies have been conducted in Asian populations. This study aimed to investigate associations between proinflammatory cytokines and lung cancer risk, considering histological types, in the Korean general population. We carried out a case-cohort study on the Korean National Cancer Center Community (KNCCC) cohort (lung cancer cases: 136, subcohort: 822). Pre-diagnostic serum levels of proinflammatory cytokines (i.e., IL-6, TNF-α, IL-1ß, IFN-γ, and IL-10) were measured using Quantikine® ELISA. A Cox proportional-hazards regression analysis was conducted. In this study, serum levels of IL-6, IL-1ß, and IFN-γ were associated with lung cancer risk. IL-6 was associated with lung cancer, regardless of the histological type. IL-1ß had an association only with adenocarcinoma, while IFN-γ had an association only with squamous-cell carcinoma. This study shows associations between serum levels of IL-6, IL-1ß, and IFN-γ and lung cancer risk, underscoring the potential of these cytokines to act as risk biomarkers. The utilization of these biomarkers for risk prediction may hold the promise of facilitating the identification of the high-risk population.

Tooth caries classification with quantitative light-induced fluorescence (QLF) images using convolutional neural network for permanent teeth in vivo.

BACKGROUND: Owing to the remarkable advancements of artificial intelligence (AI) applications, AI-based detection of dental caries is continuously improving. We evaluated the efficacy of the detection of dental caries with quantitative light-induced fluorescence (QLF) images using a convolutional neural network (CNN) model. METHODS: Overall, 2814 QLF intraoral images were obtained from 606 participants at a dental clinic using Qraypen C® (QC, AIOBIO, Seoul, Republic of Korea) from October 2020 to October 2022. These images included all the types of permanent teeth of which surfaces were smooth or occlusal. Dataset were randomly assigned to the training (56.0%), validation (14.0%), and test (30.0%) subsets of the dataset for caries classification. Moreover, masked images for teeth area were manually prepared to evaluate the segmentation efficacy. To compare diagnostic performance for caries classification according to the types of teeth, the dataset was further classified into the premolar (1,143 images) and molar (1,441 images) groups. As the CNN model, Xception was applied. RESULTS: Using the original QLF images, the performance of the classification algorithm was relatively good showing 83.2% of accuracy, 85.6% of precision, and 86.9% of sensitivity. After applying the segmentation process for the tooth area, all the performance indics including 85.6% of accuracy, 88.9% of precision, and 86.9% of sensitivity were improved. However, the performance indices of each type of teeth (both premolar and molar) were similar to those for all teeth. CONCLUSION: The application of AI to QLF images for caries classification demonstrated a good performance regardless of teeth type among posterior teeth. Additionally, tooth area segmentation through background elimination from QLF images exhibited a better performance.

Factors Affecting Disaster or Emergency Coping Skills in People with Intellectual Disabilities.

This study aimed to investigate the disaster or emergency coping skills of people with intellectual disabilities and the factors that affect these skills. The panel survey on the lives of people with disabilities from the 3rd dataset (2020) of the Korea Development Institute for the Disabled was used for this analysis. Response data from 275 people with intellectual disabilities aged 10 years or older were analyzed. Differences between disaster or emergency coping skill levels and sub-questions of skills, according to the general characteristics of people with intellectual disabilities, were identified, as well as factors affecting the level of disaster or emergency coping skills. The results show that the coping skills level was low; among the sub-questions, the use of fire extinguishers and awareness of the location of fire extinguishers or emergency bells in the event of a disaster or emergency were also low. Factors affecting the level of coping skills were found to be the level of education and experience in comprehensive disaster coping training. The results of this study suggest that training and education on disaster or emergency coping skills for people with intellectual disabilities are necessary and that programs should be developed for this purpose.

Association of Urinary Benzene Metabolite and the Ratio of Triglycerides to High-Density Lipoprotein Cholesterol: A Cross-Sectional Study Using the Korean National Environmental Health Survey (2018-2020).

The aim of this study was to investigate the association between benzene and toluene, and the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C). This cross-sectional study analyzed 1928 adults using nationally representative data from the Korean National Environmental Health Survey (KoNEHS) Cycle 4 (2018-2020). Urinary trans, trans-muconic acid (t,t-MA) and benzylmercapturic acid (BMA) were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS), and high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) were analyzed by colorimetry. Survey logistic regression analysis was applied to examine the association between urinary t,t-MA and BMA and the TG/HDL-C ratio. Urinary t,t-MA is significantly associated with an elevated TG/HDL-C ratio in both men and women (for men, OR [95% (CI)]: 2nd quartile: 2.10 [1.04, 4.22]; 3rd quartile: 2.13 [0.98, 4.62]; 4th quartile: 2.39 [1.05, 5.45]; for women, OR [95% (CI)]: 2nd quartile: 1.21 [0.71, 2.06]; 3rd quartile: 1.65 [0.94, 2.90]; 4th quartile: 1.78 [1.01, 3.11]), with significant dose-response relationships (P for trend: for men, 0.029; women, 0.024). This study shows that environmental exposure to benzene is associated with the TG/HDL-C ratio in the Korean general population. This suggests that more stringent environmental health policies are needed to reduce benzene exposure.

Association between periodontal disease and hypertriglyceridemia: Propensity score matching analysis using the 7th Korea National Health and Nutrition Examination Survey.

The prevalence of periodontitis and dyslipidemia continues to increase, and several studies have reported an association between the 2. Therefore, we assessed the relationship between periodontitis and hypertriglyceridemia using propensity score matching to efficiently address confounding factors, as well as complex sample analysis with data from Korea National Health and Nutrition Examination Survey VII (2016-2018). To match the 1:1 ratio between the groups with and without periodontitis, the propensity scores of covariates, such as age, sex, education, income, smoking, drinking, obesity, and diabetes mellitus, were calculated using logistic regression. Both results of logistic regression analysis using complex sample design for whole and matched sample after propensity score matching demonstrated a significant association between hypertriglyceridemia and periodontitis, of which the adjusted odds ratio was 1.28 (95% confidence interval = 1.10-1.50) and 1.29 (95% confidence interval = 1.09-1.52), respectively. Our findings suggest that dental healthcare workers can help raise awareness among patients with periodontitis regarding the association between periodontitis and hypertriglyceridemia, which may help them manage the condition and receive treatment.

Excellent Outcomes in Children, Adolescents, and Young Adults with Ovarian Germ Cell Tumors Treated by Either Reduced- or Standard-Dose Bleomycin.

To investigate the outcomes of children, adolescents, and young adults (AYAs) with malignant ovarian germ cell tumors (MOGCTs), we analyzed the data of 61 patients aged ≤39 years diagnosed with MOGCT between 2006 and 2022. Among 59 patients who received chemotherapy after initial diagnosis, 57 received BEP (standard dose of bleomycin with 30 units per week, n = 13) or bEP (reduced dose of bleomycin with 15 units/m2 on day 1, n = 44). The 5-year overall survival (OS) and event-free survival (EFS) rates were 98.3% and 84.9%, respectively. Reduced bleomycin dose did not adversely affect survival. Normalization of tumor markers within 3 months after surgery was significantly associated with better EFS (p < 0.01). Of the 59 surviving patients, 8 experienced surgery-related menopause, while 49 demonstrated menstrual recovery. After completion of chemotherapy, there was no significant difference in pulmonary function regarding bleomycin dose, and no overt nephrotoxicity. Approximately 60% and 25% of survivors experienced peripheral neuropathy at the end of chemotherapy and after 1 year, respectively (p < 0.01). Children and AYAs with MOGCT have favorable survival rates with minimal long-term toxicity, which are not influenced by a reduced bleomycin dose. Rapid normalization of tumor markers is associated with improved outcomes.

Ultrahigh Resolution Lipid Mass Spectrometry Imaging of High-Grade Serous Ovarian Cancer Mouse Models.

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights on how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and a triple mutant mouse models (n = 4) of high-grade serous ovarian cancer (HGSC). Lipids belonging to a total of 15 different classes were annotated and their abundance changes compared to those in healthy mouse reproductive tissue (n = 4), mapping onto major lipid pathways involved in OC progression. From intermediate-stage OC to advanced HGSC, we provide a direct visualization of lipid distributions and their biological links to inflammatory response, cellular stress, cell proliferation, and other processes. We also show the ability to distinguish tumors at different stages from healthy tissues via a number of highly specific lipid biomarkers, providing targets for future panels that could be useful in diagnosis.

Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers. METHOD: A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics. RESULTS: A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival. CONCLUSION: Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer. STUDY REGISTRATION: The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).

Control of the growth and development of murine preantral follicles in a biomimetic ovary using a decellularized porcine scaffold.

This study aimed to derive mature oocytes from murine preantral follicles cultured in a biomimetic ovary with a porcine scaffold using decellularization technology. We evaluated the DNA content and the presence of cell and extracellular matrix (ECM) components, including collagen, elastin, and glycosaminoglycans (GAGs), in decellularized (decell) porcine ovaries. The DNA content inthe decell ovarian tissues was approximately 94 % less than that in native tissues (66 ± 9.8 ng/mg vs. 1139 ± 269 ng/mg). Furthermore, the ECM component integrity was maintained in the decell ovarian tissue. The soluble collagen concentration of native ovarian tissue (native) was 195.34 ± 15.13 µg/mg (dry wt.), which was less than 878.6 ± 8.24 µg/mg for the decell ovarian tissue due to the loss of cellular mass. Hydrogels derived from decell porcine ovaries were prepared to develop an in vitro biomimetic ovary with appropriate ECM concentration (2-6 mg/mL). Scanning electron microscope (SEM) imagining revealed that the complex fiber network and porous structure were maintained in all groups treated with varying ECM concentration (2-6 mg/mL). Furthermore, rheometer analysis indicated that mechanical strength increased with ECM concentration in a dose-dependently. The preantral follicles cultured with 4 mg/mL ECM showed high rates of antral follicle (66 %) and mature oocyte (metaphase II) development (47 %). The preantral follicles cultured in a biomimetic ovary with a decell porcine scaffold showed a higher rate of antral follicle and mature oocytes than those cultured in other biomaterials such as collagen and Matrigel. In mature oocytes derived from antral follicles, meiotic spindles and nuclei were stained using a tubulin antibody and Hoechst, respectively. Two-cell embryos were developed from MII oocytes following parthenogenetic activation. Preantral follicles were cultured in a biomimetic ovary derived from the ECM of a decell porcine ovary, and embryos were generated from MII oocytes. This biomimetic ovary could contribute to restoring fertility in infertile women with reduced ovarian function, benefit mating efforts for endangered species, and maintain animals with valuable genetic traits.

Gastroesophageal reflux disease and risk of cancer: Findings from the Korean National Health Screening Cohort.

AIM: Little is known about the association of cancers other than esophageal adenocarcinoma with gastroesophageal reflux disease (GERD). This study aimed to examine the association between GERD and the risk of different types of cancer. METHODS: A cohort study was conducted using data from the National Health Screening Cohort. We included 10,261 GERD patients and 30,783 non-GERD individuals who were matched in a 1:3 ratio by age and sex. All participants were followed-up until cancer diagnosis, death, or end of the study (December 31, 2015). Hazard ratios were calculated using the Cox proportional hazards model, adjusting for smoking and alcohol consumption, physical activity, body mass index, income, area, and Charlson Comorbidity Index. RESULTS: The median follow-up time was 9.9 years. GERD was associated with an increased risk of esophageal (adjusted hazard ratios [aHR] = 3.20 [1.89-5.41]), laryngeal (aHR = 5.42 [2.68-10.96]), and thyroid cancers (aHR = 1.91 [1.55-2.34]) after controlling for all covariates. The results were consistent when examining GERD with esophagitis (K210) and without esophagitis (K219) separately. For thyroid cancer, the results were insignificant after controlling for having ever-received thyroid biopsy procedures. A dose-response relationship was found between GERD and esophageal cancer as well as laryngeal cancer, with patients with a longer duration of GERD treatment showing a stronger effect. In contrast, GERD was associated with a reduced risk of colorectal (aHR = 0.73 [0.59-0.90]), liver (aHR = 0.67 [0.51-0.89]), and pancreatic cancers (aHR = 0.43 [0.24-0.76]), which might have resulted from differences in healthcare utilization between GERD and non-GERD groups. CONCLUSION: GERD was associated with an increased risk of esophageal and laryngeal cancers. Additionally, early detection and treatment of precancerous lesions among the GERD group could lead to a lower risk of colorectal, liver, and pancreatic cancers.