Cytoreductive surgery (CRS) is the most important treatment method that increases survival in advanced-stage ovarian cancer (OC) patients. However, complications after CRS are seen as a significant cause of morbidity and mortality. Preoperative risk assessment of patients is of great importance. In recent years, inflammatory markers have been the subject of many studies evaluating malignancy and surgical outcomes. Ca125, Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), Monocyte-lymphocyte ratio (MLR), systemic inflammation index (SII), and systemic inflammatory response index (SIRI) stand out as prognostic and predictive tools in malignancies. This study aims to evaluate the preoperative inflammatory markers in patients who underwent CRS for advanced-stage epithelial ovarian cancer and to investigate the predictive power of postoperative complications.

This retrospective study examines patients who underwent CRS due to advanced-stage epithelial OC at Sakarya University Training and Research Hospital between 2014 and 2023. Postoperative complications of the patients were graded according to the Clavien-Dindo classification (CDC); Ca125, NLR, PLR, SII, SIRI and MLR values were calculated using preoperative laboratory data, and the predictive values of inflammatory markers were analysed with ROC curves.

A significant relationship was found between complications with CDC ≥ 3 and NLR, PLR, MLR, SII, and SIRI. The AUC value of SII was calculated as 0.740 (p < 0.001), NLR as 0.719 (p = 0.001), PLR as 0.668 (p = 0.011), and SIRI as 0.651 (p = 0.022). SII stands out as the marker with the highest predictive power. SII is a strong marker in predicting postoperative complications, especially in advanced-stage OC patients.

It was shown that preoperative inflammation markers may be an effective method for predicting postoperative complications in advanced-stage OC patients undergoing CRS. These findings may contribute to optimising surgical management and reducing complications. In future studies, these markers should be evaluated in groups with more patients, and their predictive power should be investigated.

Hypoxia-Inducible Factor-1α (HIF-1α) is crucial in the progression of ovarian cancer, especially in influencing its tumor microenvironment and promoting pathogenic pathways that worsen female infertility. In hypoxic settings, HIF-1α is stabilized and activates the transcription of genes associated with angiogenesis, metabolic reprogramming, epithelial-to-mesenchymal transition, and therapeutic resistance. Angiogenesis and glycolytic reprogramming mediated by HIF-1 tumor proliferation, survival, and metastasis. Its dysfunction concurrently impairs ovarian homeostasis, undermining follicular growth, hormone synthesis, and the ovarian vascular network, consequently contributing to infertility. Moreover, HIF-1α induces persistent inflammation and oxidative stress, promoting an environment damaging to reproductive health. Due to its dual function in ovarian cancer growth and infertility, HIF-1α is a potential therapeutic target. Strategies including small molecule inhibitors and nanoparticle-mediated delivery of drugs possess the potential to reduce HIF-1α activity, hence reducing cancer progression while protecting fertility. This review seeks to clarify the molecular basis of HIF-1α in ovarian cancer and its effects on female infertility, providing insights into novel treatment approaches that target both controlling the disease and preserving fertility.

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, largely due to its late-stage diagnosis and high recurrence rates. Chronic inflammation is a critical driver of OC progression, contributing to immune evasion, tumor growth, and metastasis. Inflammatory cytokines, including IL-6, TNF-α, and IL-8, as well as key signaling pathways such as nuclear factor kappa B (NF-kB) and signal transducer and activator of transcription 3 (STAT3), are upregulated in OC, promoting a tumor-promoting environment. The tumor microenvironment (TME) is characterized by immune cells like tumor-associated macrophages (TAMs) and regulatory T cells (Tregs), which suppress anti-tumor immune responses, facilitating immune evasion. Furthermore, OC cells utilize immune checkpoint pathways, including PD-1/PD-L1, to inhibit cytotoxic T cell activity. Targeting these inflammatory and immune evasion mechanisms offers promising therapeutic strategies. COX-2 inhibitors, Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway blockers, and NF-kB inhibitors have shown potential in preclinical studies, while immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 have been explored with mixed results in OC. Additionally, emerging research on the microbiome and inflammation-related biomarkers, such as microRNAs (miRNAs) and exosomes, points to new opportunities for early detection and precision medicine. Future approaches to OC treatment must focus on personalized strategies that target the inflammatory TME, integrating anti-inflammatory therapies with immunotherapy to enhance patient outcomes. Continued research into the interplay between inflammation and immune evasion in OC is essential for developing effective, long-lasting treatments.

Ovarian cancer (OC) is one among most significantly fatal gynecological cancers, with late-stage detection and an inadequate prognosis. Plasminogen activator inhibitor-1 ( PAI1 ) gene anticipates negative outcomes in many different kinds of malignancies. Several research investigations are currently being done to examine the biological role of PAI1 in OC and the possible benefits of targeted pharmacotherapies. The PAI1 gene has been linked to the emergence and development of cancer in the ovary. PAI1 , an inhibitor of serine protease, influences the fibrinolysis and extracellular matrix remodeling, both of which are crucial for tumor expansion and metastatic growth. PAI1 levels have been discovered to be subsequently more elevated in malignant ovarian tissues than in usual ovarian tissue, demonstrating a potential connection among PAI1 overexpression and OC development. PAI1 promotes tumor cell proliferation, movement, and an invasion by influencing the urokinase-plasminogen activators and through interactions with cell surface receptors. In addition, PAI1 gene contributes to angiogenesis and apoptotic cell death, which contribute to the more hostile phenotypes of OC. The prognostic and therapeutic consequences of focusing on PAI1 in OC are explored, demonstrating PAI1 's potential to be a biomarker and emphasizing for novel treatment approaches. The PAI1 gene possesses several functions in OC, affecting tumor development, an invasion, and metastatic growth. Comprehending the complicated interactions and mechanisms that regulate PAI1 in OC may lead to more efficient evaluation and treatment strategies and ultimately enhance patient outcomes.

Introduction Evidence suggests inflammation plays a key role in the development of ovarian malignancy. This study investigated the relationship between the C-reactive protein (CRP) to serum albumin (Alb) ratio and clinicopathological parameters in ovarian cancer patients. The goal was to determine if this readily measurable inflammatory marker could provide insights into disease severity. Methods A prospective study of 94 patients with histopathologically confirmed ovarian cancer (diagnosed between November 2020 and December 2023) investigated the relationship between the pretreatment C-reactive protein to albumin ratio (CRP/Alb), and various clinicopathological characteristics, including age, distant metastasis, lymph node involvement, ascites, tumor grade, and surgical stage. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic accuracy of the CRP/Alb ratio and establish a cutoff value. Results Patients with metastasis, lymph node involvement, ascites, higher tumor grade, and advanced stages (III and IV) had significantly higher median CRP/Alb ratios compared to those without these features (1.43 vs. 0.78, 1.47 vs. 0.51, 1.16 vs. 0.46, 1.46 vs. 0.52, and stages I/II (0.49/0.95) vs. stages III/IV (1.47/1.58), respectively; all p < 0.001). ROC analysis determined an optimal cutoff value of 1.08. A preoperative CRP/Alb ratio above this cutoff indicated severe disease based on clinicopathological parameters. Conclusion In conclusion, elevated pretreatment CRP/Alb ratios correlated with more severe and advanced ovarian cancer.

The preoperative prognostic nutritional index (PPNI) has been investigated as a prognostic indicator in various cancers including epithelial ovarian cancer (EOC). However, its prognostic relevance in epithelial ovarian clear cell cancer (EOC-CC) remains uncertain. The objective of the study was to clarify the prognostic values of PPNI in EOC-CC patients.

We retrospectively reviewed 290 EOC-CC patients who underwent staging surgery at Rajavithi Hospital between January 2008 and December 2019. The PPNI was calculated using serum albumin × 10 (g/L) + 0.005 × peripheral blood lymphocyte count (per mm3). The association between PPNI and survival outcome was analyzed using the Kaplan-Meier method and the Cox proportional hazard model.

The optimal cut-off value of PPNI, set at a mean of PPNI as 50, divided the EOC-CC patients into two groups: the low (n = 115) and the high (n = 175) PPNI group. With a median follow-up time of 63 months, patients with high PPNI exhibited significantly superior 5-year overall survival (OS) rates (76.4% vs. 56.8%, P = 0.004) and 5-year progression-free survival (PFS) rates (71.0% vs. 58.7%, P = 0.017) compared to patients with low PPNI. Univariate analysis revealed high PPNI correlated with increased OS (hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.35 - 0.75) and PFS (HR: 0.63; 95% CI: 0.43 - 0.92). Nevertheless, in a multivariate analysis, high PPNI did not retain its status as an independent prognostic factor for a favorable prognosis in EOC-CC patients.

The present study did not confirm the prognostic significance of PPNI on survival outcomes in EOC-CC patients. Therefore, conducting prospective clinical research with large samples is necessary to illustrate the predictive values of PPNI in this rare disease.

Endometriosis is a benign disease but with malignant behavior, sharing numerous features with cancers. Endometriosis is the development of endometrial tissue outside the uterus, with the presence of both glands and stroma. Approximately 10% of women of reproductive age suffer from endometriosis; it involves high social costs and affects the patient's quality of life. In this review, we attempt to capture the pathogenesis mechanisms that are common to endometriosis and cancer based on molecular biology, focusing more on the principle of immunological changes and stemness. Clinical applicability will consist of targeted treatments that represent future directions in these diseases, which impose a burden on the healthcare system. Unlike endometriosis, cancer is a disease with fatal evolution, with conventional treatment based on chemo/radiotherapy. Here, we focus on the niche of personalized treatments that target molecular pathways. Our findings show that, in both pathologies, the resistance to treatments is due to the stemness of the stem cells, which might play a role in the appearance and evolution of both diseases. More research is needed before we can draw firm conclusions.

Cancer remains a global health challenge, prompting a search for effective treatments with fewer side effects. Thymol, a natural monoterpenoid phenol derived primarily from thyme (Thymus vulgaris) and other plants in the Lamiaceae family, is known for its diverse biological activities. It emerges as a promising candidate in cancer prevention and therapy. This study aims to consolidate current research on thymol's anticancer effects, elucidating its mechanisms and potential to enhance standard chemotherapy, and to identify gaps for future research. A comprehensive review was conducted using databases like PubMed/MedLine, Google Scholar, and ScienceDirect, focusing on studies from the last 6 years. All cancer types were included, assessing thymol's impact in both cell-based (in vitro) and animal (in vivo) studies. Thymol has been shown to induce programmed cell death (apoptosis), halt the cell division cycle (cell cycle arrest), and inhibit cancer spread (metastasis) through modulation of critical signaling pathways, including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinase (ERK), mechanistic target of rapamycin (mTOR), and Wnt/β-catenin. It also enhances the efficacy of 5-fluorouracil (5-FU) in colorectal cancer treatments. Thymol's broad-spectrum anticancer activities and non-toxic profile to normal cells underscore its potential as an adjunct in cancer therapy. Further clinical trials are essential to fully understand its therapeutic benefits and integration into existing treatment protocols.

Ovarian cancer survival among Black women is the lowest across all racial and ethnic groups. Poor dietary quality also disproportionately affects Black populations, but its association with ovarian cancer survival in this population remains largely unknown.

To examine associations between dietary patterns and survival among Black women diagnosed with epithelial ovarian cancer (EOC).

This prospective cohort study was conducted among self-identified Black women aged 20 to 79 years newly diagnosed with histologically confirmed EOC in the African American Cancer Epidemiology Study (AACES) between December 2010 and December 2015, with follow-up until October 2022. AACES is a population-based study of ovarian cancer risk and survival among Black women in 11 US regions. Data were analyzed from March 2023 to June 2024.

Dietary patterns were assessed by the Healthy Eating Index-2020 (HEI-2020) and Alternative Healthy Eating Index-2010 (AHEI-2010), with scores calculated based on dietary intake in the year prior to diagnosis and collected via the validated Block 2005 Food Frequency Questionnaire. Higher scores indicate better dietary quality.

Hazard ratios (HRs) and 95% CIs were estimated from multivariable Cox models for the association between adherence to dietary recommendations and overall mortality among all participants and those with high-grade serous ovarian cancer (HGSOC).

Among 483 Black women with EOC (mean [SD] age, 58.1 [10.5] years), 310 deaths were recorded during a median (IQR) follow-up of 4.3 (2.0-8.2) years. No association of dietary patterns with mortality was found among women with EOC overall. However, among 325 women with HGSOC, better adherence to HEI-2020 was associated with decreased mortality in later quartiles compared with the first quartile (HR, 0.63; 95% CI, 0.44-0.92 for quartile 2; HR, 0.67; 95% CI, 0.46-0.97 for quartile 3; HR, 0.63; 95% CI, 0.44-0.91 for quartile 4 ). Similar results were observed with AHEI-2010 among women with HGSOC for the second (HR, 0.62; 95% CI, 0.43-0.89) and fourth (HR, 0.67; 95% CI, 0.45-0.98) quartiles compared with quartile 1.

In this study, women with moderate and high prediagnosis dietary quality had significantly lower mortality rates from HGSOC compared with women with the lowest prediagnosis dietary quality. These findings suggest that even moderate adherence to dietary guidelines prior to diagnosis may be associated with improved survival among Black women with HGSOC, the most lethal form of ovarian cancer.

Epidemiological studies show that radon and cigarette smoke interact in inducing lung cancer, but the contribution of nicotine in response to alpha radiation emitted by radon is not well understood.

Bronchial epithelial BEAS-2B cells were either pre-treated with 2 µM nicotine during 16 h, exposed to radiation, or the combination. DNA damage, cellular and chromosomal alterations, oxidative stress as well as inflammatory responses were assessed to investigate the role of nicotine in modulating responses.

Less γH2AX foci were detected at 1 h after alpha radiation exposure (1-2 Gy) in the combination group versus alpha radiation alone, whereas nicotine alone had no effect. Comet assay showed less DNA breaks already just after combined exposure, supported by reduced p-ATM, p-DNA-PK, p-p53 and RAD51 at 1 h, compared to alpha radiation alone. Yet the frequency of translocations was higher in the combination group at 27 h after irradiation. Although nicotine did not alter G2 arrest at 24 h, it assisted in cell cycle progression at 48 h post radiation. A slightly faster recovery was indicated in the combination group based on cell viability kinetics and viable cell counts, and significantly using colony formation assay. Pan-histone acetyl transferase inhibition using PU139 blocked the reduction in p-p53 and γH2AX activation, suggesting a role for nicotine-induced histone acetylation in enabling rapid DNA repair. Nicotine had a modest effect on reactive oxygen species induction, but tended to increase alpha particle-induced pro-inflammatory IL-6 and IL-1β (4 Gy). Interestingly, nicotine did not alter gamma radiation-induced γH2AX foci.

This study provides evidence that nicotine modulates alpha-radiation response by causing a faster but more error-prone repair, as well as rapid recovery, which may allow expansion of cells with genomic instabilities. These results hold implications for estimating radiation risk among nicotine users.

Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.5% were diagnosed in late stages (FIGO IIb-IV), and 73.5% had high-grade serous OC (HGSOC). Minor allele frequencies in controls were 9.2% for rs11556218 (G allele), 13.7% for rs4778889 (C allele), 10.4% for rs4072111 (T allele), and 32.3% for rs1131445 (C allele). We found significant associations of rs11556218 (G vs. T allele: OR 2.76, 95% CI 1.84-4.14, p < 0.0001) with elevated OC risk in the whole cohort (p < 0.001) and in both premenopausal (p < 0.001) and postmenopausal (p = 0.001) subgroups. These associations remained significant across heterozygote (p < 0.001), dominant (p < 0.001), and overdominant (p < 0.001) models. IL-16 rs4778889 was associated with OC risk predominantly in premenopausal women (p < 0.0001 in almost all models). In the whole cohort, the C allele was associated with OC risk (OR 1.54, CI 95% 1.06-2.23, p = 0.024), and the association of rs4778889 was significant in dominant (p = 0.019), overdominant (p = 0.033), and heterozygote (p = 0.027) models. Furthermore, rs4778889 was linked with HGSOC (p = 0.036) and endometriosis-related OC subtypes (p = 0.002). No significant associations were found for rs4072111 or rs1131445 (p = 0.81 or 0.47, respectively). In conclusion, rs11556218 and rs4778889 SNPs are associated with OC risk, especially in premenopausal women.

To investigate the relationship between the changes of C-reactive protein to Albumin Ratio (CAR) levels and Interval Debulking Surgery (IDS) outcome after Neoadjuvant Chemotherapy (NAC) in ovarian cancer patients.

A nested case-control study for 209 patients with ovarian cancer who received NAC-IDS therapy from the First Affiliated Hospital of Bengbu Medical College between 2015‒2021 was conducted. Demographic data, laboratory indicators, and imaging examinations were collected. The outcome was regarded as optimal IDS in this study. Univariate and multivariate logistic regression analyses were performed to assess the relationship of CAR before NAC, CAR after NAC and ∆CAR with optimal IDS. The authors also performed the subgroup analysis based on menopausal state.

The end time of follow-up was January 24, 2022. A total of 156 patients had been treated with optimal IDS, and 53 with suboptimal IDS. After adjusting age, body mass index, menopausal state, NAC drug, peritoneal perfusion and CAR before NAC, the result showed that CAR after NAC (Odds Ratio [OR = 3.48], 95% Confidence Interval [95% CI 1.28‒9.48], p = 0.015) and ∆CAR (OR = 0.29, 95% CI 0.11‒0.78, p = 0.015) were associated with optimal IDS, respectively. Additionally, the authors found a significant correlation between CAR after NAC and optimal IDS (OR = 3.16, 95% CI 1.07‒9.35, p = 0.038), and ∆CAR and optimal IDS (OR = 0.32, 95% CI 0.11‒0.94, p = 0.038) among ovarian cancer patients with menopause.

CAR after NAC and ∆CAR were independent prognostic markers of optimal interval debulking surgery for ovarian cancer patients.

Endometriosis (EMS) is an oestrogen-dependent, chronic disease affecting women of a reproductive age. One of the important factors involved in the development of this disease is the complex disorders associated with the functioning of the immune system. Recent evidence has shown that EMS development is associated with changes in systemic and local immunity, including functional disturbances of effector and antigen-presenting cells. One of the reasons for immune imbalance can be the improper expression of immune checkpoints (ICPs). ICPs and their ligands are responsible for maintaining self-tolerance and the modulation of the initiation, duration, and magnitude of the immune response of effector cells in normal tissues to avoid tissue damage. Considering the complex nature of co-stimulatory or co-inhibitory ICPs and the signalling between effector cells and APCs, we hypothesise that changes in cells' activity caused by ICPs may lead to serious immune system disturbances in patients with endometriosis. Moreover, both upregulation and downregulation in the expression of ICPs may be implicated in this process, including the reduced activity of effector cells against endometrial implants and disturbances in the antigen-presenting process. In this narrative review, we discuss, for the first time, key findings from the emerging literature, describing the associations between ICPs and their possible implication in the pathogenesis of endometriosis.

The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.

Studies on association between low-dose aspirin use and ovarian cancer risk were mostly based on self-reported medication use and few had large enough sample size to investigate the potential modification effect by ovarian cancer risk factors.

In these two nationwide nested case-control studies among the Danish and Swedish female population, 11,874 women with ovarian cancer (30-84 years old) (Denmark: 7328 diagnosed in 2000-2019, Sweden: 4546 diagnosed in 2010-2018) were randomly age- matched with 473,960 female controls (293,120 from Denmark, and 181,840 from Sweden). We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) and combined the estimates based the fixed-effect assumption. Effect modification by inflammation-related risk factors and by indication (cardiovascular disease, CVD) were also investigated.

Ever use of low-dose aspirin was not strongly associated with the overall risk of ovarian cancer (OR = 0.97; 95%CI: 0.92-1.03). However, the association differed according to parity (nulliparous: OR = 0.80, 95%CI: 0.70-0.92; parous: OR = 1.00, 95%CI: 0.94-1.07; p-interaction = 0.0024), and according to history of CVD (no CVD: OR = 0.91, 95%CI: 0.82-1.00; ever CVD: OR = 1.05, 95%CI: 0.97-1.13; p-interaction =0.0204).

Low-dose aspirin use was associated with a decreased ovarian cancer risk especially in nulliparous women and in women without CVD diagnosis.

Women with an inherited pathogenic variant in BRCA1 or BRCA2 have a greatly increased risk of developing ovarian cancer, but the importance of behavioral factors is less clear. We used a case-only design to compare the magnitude of associations with established reproductive, hormonal, and lifestyle risk factors between BRCA mutation carriers and noncarriers.

We pooled data from five studies from the Ovarian Cancer Association Consortium including 637 BRCA carriers and 4,289 noncarriers. Covariate-adjusted generalized linear mixed models were used to estimate interaction risk ratios (IRR) and 95% confidence intervals (CI), with BRCA (carrier vs. noncarrier) as the response variable.

IRRs were above 1.0 for known protective factors including ever being pregnant (IRR = 1.29, 95% CI; 1.00-1.67) and ever using the oral contraceptive pill (1.30, 95% CI; 1.07-1.60), suggesting the protective effects of these factors may be reduced in carriers compared with noncarriers. Conversely, the IRRs for risk factors including endometriosis and menopausal hormone therapy were below 1.0, suggesting weaker positive associations among BRCA carriers. In contrast, associations with lifestyle factors including smoking, physical inactivity, body mass index, and aspirin use did not appear to differ by BRCA status.

Our results suggest that associations with hormonal and reproductive factors are generally weaker for those with a pathogenic BRCA variant than those without, while associations with modifiable lifestyle factors are similar for carriers and noncarriers.

Advice to maintain a healthy weight, be physically active, and refrain from smoking will therefore benefit BRCA carriers as well as noncarriers.

Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, 2 patient cohorts were enrolled: patients with OvCa who underwent a diagnostic or cytoreductive surgery and nononcological patients, who underwent abdominal surgery for benign gynecological conditions and acted as the control group. Systematic extraction of PFD-sEVs from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage, and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEV proteomic profiles in high-grade serous ovarian carcinomas (HGSOCs) revealed 2 clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of PFD-sEV content provided a prognostic value with potential implications in HGSOC clinical management.

The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022. Our study included 36 study participants with ovarian cancer who provided biospecimens; 20 randomly selected White patients and all 16 eligible Black patients, aged 50-70 years. Acylcarnitines (n = 45 species), sphingomyelins (n = 34), and ceramides (n = 21) were assayed on cervicovaginal fluid, while four cytokines (IL-1β, IL-10, TNF-α, and IL-6) were assayed on saliva. Seven metabolites showed >2-fold differences, two showed significant differences using the Wilcoxon rank-sum test (p < 0.05; False Discovery Rate > 0.05), and 30 metabolites had coefficients > ±0.1 in a Penalized Discriminant Analysis that achieved two distinct clusters by race. Arachidonoylcarnitine, the carnitine adduct of arachidonic acid, appeared to be consistently different by race. Thirty-eight vaginal fluid metabolites were significantly correlated with systemic inflammation biomarkers, irrespective of race. These findings suggest that vaginal fluid metabolites may differ by race, are linked with systemic inflammation, and hint at a potential role for mitochondrial dysfunction and sphingolipid metabolism in OC disparities. Larger studies are needed to verify these findings and further establish specific biological mechanisms that may link the vaginal microbiome with OC racial disparities.

Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes.

In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020.

We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively.

Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery.

To investigate whether paracetamol use is associated with a reduced risk of epithelial ovarian cancer (EOC).

A nationwide nested case-control study.

Danish female population.

A total of 9589 EOC cases diagnosed from 2000 to 2019 were age-matched with 383 549 randomly selected female controls using risk set sampling.

Paracetamol use, reproductive history, history of medication and history of surgery were retrieved from Danish national registers. Paracetamol use was defined as at least two prescriptions for up to 1 year before the index date, and was further classified according to recency, duration, cumulative dose and intensity of dose.

Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between paracetamol and EOC risk, overall and by histological subtypes.

'Ever' use of paracetamol was associated with a reduced EOC risk after adjusting for potential confounding factors (OR 0.92, 95% CI 0.87-0.97). The association was only significant among recent users (OR 0.89, 95% CI 0.84-0.95). The risk declined further with the increasing level of cumulative dose and intensity; women from the group with a high cumulative dose and a high intensity had a 13% (OR 0.87, 95% CI 0.80-0.94) and 14% (OR 0.86, 95% CI 0.79-0.93) reduced risk, respectively. In the histological subtype analysis, reduced risk with 'ever' use was most pronounced for serous and clear cell tumours.

Paracetamol use was associated with a decreased risk of EOC in a dose-response manner. Future studies are needed to validate the findings and investigate the mechanisms behind the association.

The purpose of this study was to assess the risks of hyperthyroidism and hypothyroidism related to gynecological cancers. Population-based retrospective cohort study. We conducted a cohort study using the Taiwan National Health Insurance Research Database to explore hyperthyroidism and hypothyroidism associated with site-specific gynecologic cancers in women from January 1, 2000 to December 31, 2018. The examined gynecologic cancers included endometrial (EC), uterine corpus cancer (UC), and ovarian cancer (OC). The incidence and hazard ratios were quantified using Cox proportional hazards models. The incidence of developing gynecological (Gyn) cancers in the hyperthyroid and hypothyroid women was 0.29 and 0.44 per 1000 person-years, which was 0.86 fold lower and 1.13 fold higher than that in the comparison cohort (p < 0.001). Compared with patients aged 20-40 years, patients in older age groups had a lower and higher risk of developing Gyn cancers (for hyperthyroid, 40-65 years: adjusted hazard ratio (aHR) = 0.82; > 65 years: aHR = 0.94; for hypothyroid, adjusted hazard ratio (aHR) = 1.26; > 65 years: aHR = 1.38). Compared with the non-hypothyroid women and non-hyperthyroid women beyond 6 years of follow-up, hypothyroid and hyperthyroid women showed decreased risk of Gyn cancers. Medication treatment for hyperthyroid and hypothyroid disease did not showed significant association in subgroup analyses (aHR = 0.99 and 0.80, respectively). Our results show that women with hyperthyroidism have a significantly reduced risk of gynecological cancers, whereas women with hypothyroidism have a slightly increased risk of gynecological cancers suggesting an association between thyroid function level and risk of gynecological cancers.

Copper (Cu) is an essential micronutrient for the correct development of eukaryotic organisms. This metal plays a key role in many cellular and physiological activities, including enzymatic activity, oxygen transport, and cell signaling. Although the redox activity of Cu is crucial for enzymatic reactions, this property also makes it potentially toxic when found at high levels. Due to this dual action of Cu, highly regulated mechanisms are necessary to prevent both the deficiency and the accumulation of this metal since its dyshomeostasis may favor the development of multiple diseases, such as Menkes' and Wilson's diseases, neurodegenerative diseases, diabetes mellitus, and cancer. As the relationship between Cu and cancer has been the most studied, we analyze how this metal can affect three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis. Gynecological diseases are characterized by high prevalence, morbidity, and mortality, depending on the case, and mainly include benign and malignant tumors. The cellular processes that promote their progression are affected by Cu, and the mechanisms that occur may be similar. We analyze the crosstalk between Cu deregulation and gynecological diseases, focusing on therapeutic strategies derived from this metal.

 To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses.

 We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry.

 Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks.

 The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

This review aimed to describe the potential for therapeutic targeting of the JAK/STAT signaling pathway by repurposing the clinically-approved JAK inhibitor ruxolitinib in the patients with epithelial ovarian cancer (OC) setting.

We reviewed publications that focus on the inhibition of the JAK/STAT pathway in hematological and solid malignancies including OC.

Preclinical studies showed that ruxolitinib effectively reduces OC cell viability and metastasis and enhances the anti-tumor activity of chemotherapy drugs. There are a number of recent clinical trials exploring the role of JAK/STAT inhibition in solid cancers including OC. Early results have not adequately supported efficacy in solid tumors. However, there are preclinical data and clinical studies supporting the use of ruxolitinib in combination with both chemotherapy and other targeted drugs in OC setting.

Inflammatory conditions and persistent activation of the JAK/STAT pathway are associated with tumourigenesis and chemoresistance, and therapeutic blockade of this pathway shows promising results. For women with OC, clinical investigation exploring the role of ruxolitinib in combination with chemotherapy agents or other targeted therapeutics is warranted.

Ovarian cancer (OC) is one of the most lethal gynecological malignancies. The use of biological compounds such as non-coding RNAs (ncRNAs) is being considered as a therapeutic option to improve or complement current treatments since the deregulation of ncRNAs has been implicated in the pathogenesis and progression of OC. Old drugs with antitumoral properties have also been studied in the context of cancer, although their antitumor mechanisms are not fully clear. For instance, the antidiabetic drug metformin has shown pleiotropic effects in several in vitro models of cancer, including OC. Interestingly, metformin has been reported to regulate ncRNAs, which could explain its diverse effects on tumor cells. In this review, we discuss the mechanism of epigenetic regulation described for metformin, with a focus on the evidence of metformin-dependent microRNA (miRNAs) and long non-coding RNA (lncRNAs) regulation in OC.

A study of tumor resectability in pre-operative patients with advanced epithelial ovarian cancer is required to predict primary surgical benefits accurately. This study aims to investigate IL6, CA-125 and HE4 to predict tumor resectability in the pre-operative patients with advanced epithelial ovarian cancer.

This cross-sectional study was conducted in the polyclinic, oncology and gynecology inpatient room of Dr. M. Jamil Padang Hospital from June until December 2022. Advanced epithelial ovarian cancer stage based on histology result from FIGO stages IIIB-IVA. IL6, CA-125, and HE4 were measured using ECLIA (electrochemiluminescence immunoassay). Categorical data were assessed using Chi-square and Mann-Whitney tests. Numerical variable correlations were analyzed using Pearson Correlation tests. While the correlation between numerical and nominal variables was analyzed using the Eta correlation test. A p-value of <0,05 was considered a significant correlation. The cut-off value of serum IL6, CA-125, and HE4 was determined with a ROC curve. The sensitivity and specificity of each clinical parameter were calculated.

There was a significant difference in IL-6 (1328 vs 752 pg/ml; p<0,001), CA-125 (1260,5 vs 819,5 U/ml; p<0,001), and HE4 levels (1320 vs 760 pmol/L; p<0,001) between patients with tumor resectability of > 1 cm (suboptimal) vs < 1 cm (optimal). There was a correlation between IL6 (r = 0,832), CA-125 (r = 0,716), and HE4 (r = 0,716) with tumor resectability.

Measuring IL6, CA-125, and HE4 levels is useful for clinicians to predict tumor resectability in pre-operative patients with advanced epithelial ovarian cancer.

One of the mechanisms of ovarian tumorigenesis is through inflammation. Kidney dysfunction is associated with increased inflammation; thus, we assessed its relationship with ovarian cancer risk.

In prospectively collected samples, we evaluated the association of kidney function markers and C-reactive protein (CRP) with ovarian cancer risk in the UK Biobank. We used multivariable-adjusted Cox proportional hazards models to evaluate quartiles of serum and urine markers with ovarian cancer risk overall and by histology. We assessed effect modification by CRP (≤3.0, >3.0 mg/L).

Among 232,908 women (1,110 ovarian cancer cases diagnosed from 2006-2020), we observed no association between estimated glomerular filtration rate and ovarian cancer risk (Q4 vs. Q1: HR, 1.00; 95% confidence intervals, 0.83-1.22). Potassium was associated with endometrioid (Q4 vs. Q1: 0.33, 0.11-0.98) and clear cell (4.74, 1.39-16.16) tumors. Poor kidney function was associated with a nonsignificant increase in ovarian cancer risk among women with CRP>3.0 mg/L (e.g., uric acid Q4 vs. Q1; 1.23, 0.81-1.86), but not CRP≤3.0 mg/L (0.83, 0.66-1.05). Other associations did not vary across CRP categories.

Kidney function was not clearly associated with ovarian cancer risk. Larger studies are needed to evaluate possible histology specific associations. Given the suggestive trend for increased ovarian cancer risk in women with poor kidney function and high CRP, future work is needed, particularly in populations with a high prevalence of inflammatory conditions.

This study provided the first evaluation of markers of kidney function in relation to ovarian cancer risk.

Malignant ascites is prevalent in advanced-stage ovarian cancer and may facilitate identification of the drivers of muscle loss. This study aimed to evaluate the association of ascites with changes in systemic inflammation and muscle after treatment of advanced-stage ovarian cancer.

We evaluated 307 patients with advanced-stage (III/IVA) ovarian cancer who underwent primary debulking surgery and adjuvant platinum-based chemotherapy between 2010 and 2019. The changes in skeletal muscle index (SMI) and radiodensity (SMD) were measured using pre-surgery and post-chemotherapy portal-venous phase contrast-enhanced computed tomography scans at L3. Systemic inflammation was measured using albumin levels, prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR). Primary endpoint was the changes in SMI and SMD after treatment. Linear regression analysis was used to test associations between muscle change and other covariates. Mediation analysis was used to determine the mediator.

The median (range) age was 53 (23-83) years. The median duration (range) of follow-up was 5.2 (1.1-11.3) years. Overall, 187 (60.9%) patients had ascites. The changes in muscle and systemic inflammatory markers after treatment were significantly different between patients with and without ascites (SMI: -3.9% vs. 2.2%, P < 0.001; SMD: -4.0% vs. -0.4%, P < 0.001; albumin: -4.4% vs. 2.1%, P < 0.001; PNI: -8.4% vs. -0.1%, P < 0.001; NLR: 20.6% vs. -29.4%, P < 0.001; and PLR: 1.7% vs. -19.4%, P < 0.001). The changes in SMI and SMD were correlated with the changes in albumin, PNI, NLR, and PLR (all P < 0.001). In multiple linear regression, ascites and NLR changes were negatively while albumin change was positively correlated with SMI change (ascites: β = -3.19, P < 0.001; NLR change: β = -0.02, P = 0.003; albumin change: β = 0.37, P < 0.001). Ascites and NLR changes were negatively while PNI change was positively correlated with SMD change (ascites: β = -1.28, P = 0.02; NLR change: β = -0.02, P < 0.001; PNI change: β = 0.11, P = 0.04). In mediation analysis, ascites had a direct effect on SMI change (P < 0.001) and an indirect effect mediated by NLR change (indirect effects = -1.61, 95% confidence interval [CI]: -2.22 to -1.08) and albumin change (indirect effects = -2.92, 95% CI: -4.01 to -1.94). Ascites had a direct effect on SMD change (P < 0.001) and an indirect effect mediated by NLR change (indirect effects = -1.76, 95% CI: -2.34 to -1.22) and PNI change (indirect effects = -2.00, 95% CI: -2.79 to -1.36).

Malignant ascites was associated with enhanced systemic inflammation and muscle loss after primary debulking surgery and adjuvant chemotherapy in advanced-stage ovarian cancer. The association between ascites and muscle loss may be mediated by systemic inflammation.

The development of multidrug resistance (MDR) against chemotherapeutic agents has become a major impediment in cancer therapy. Understanding the underlying mechanism behind MDR can guide future treatment for cancer with better therapeutic outcomes. Recent studies evidenced that crossroads interaction between the heat shock proteins (HSP) and inflammatory responses under the tumor microenvironment plays a pivotal role in modulating drug responsiveness and drug resistance through a complex cytological process. This review aims to investigate the interrelationship between inflammation and HSP in acquiring multiple drug resistance and investigate strategies to overcome the drug resistance to improve the efficacy of cancer treatment. HSP plays a dual regulatory effect as an immunosuppressive and immunostimulatory agent, involving the simultaneous blockade of multiple signaling pathways in acquiring MDR. For example, HSP27 shows biological effects on monocytes by causing IL10 and TNFα secretion and blocking monocyte differentiation to normal dendritic cells and tumor-associated macrophages to promote cancer progression and chemoresistance. Thus, the HSP function and immune-checkpoint release modalities provide a therapeutic target for a therapeutically beneficial approach for enhancing anti-tumor immune responses. The interconnection between inflammation and HSP, along with the tumor microenvironment in acquiring drug resistance, has become crucial for rationalizing the effect of HSP immunomodulatory activity with immune checkpoint blockade. This relationship can overcome drug resistance and assist in the development of novel combinatorial cancer immunotherapy in fighting cancer with decreasing mortality rates.

Explainable Artificial Intelligence (XAI) enables a holistic understanding of the complex and nonlinear relationships between genes and prognostic outcomes of cancer patients. In this study, we focus on a distinct aspect of XAI - to generate accurate and biologically relevant hypotheses and provide a shorter and more creative path to advance medical research. We present an XAI-driven approach to discover otherwise unknown genetic biomarkers as potential therapeutic targets in high-grade serous ovarian cancer, evidenced by the discovery of IL27RA, which leads to reduced peritoneal metastases when knocked down in tumor-carrying mice given IL27-siRNA-DOPC nanoparticles.

Explainable Artificial Intelligence is amenable to generating biologically relevant testable hypotheses despite their limitations due to explanations originating from post hoc realizations.

(1) The degree of cytoreduction achieved during primary debulking surgery (PDS) is an important prognostic factor for the survival of patients with epithelial ovarian cancer (EOC). Our aim was to investigate the prognostic value of preoperative laboratory parameters for the outcome of PDS. (2) We analyzed the preoperative laboratory parameters of 150 serous EOC patients who underwent PDS between 2006 and 2013. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values of the variables for predicting the PDS outcome. We used binary logistic regression to examine the independent predictive value of the factors for incomplete cytoreduction. (3) Among the parameters, we established optimal cut-off values for cancer antigen (Ca)-125, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) to predict the outcome of PDS. The results of binary logistic regression showed that stage (FIGO III-IV), MLR (>0.305), and Ca-125 (>169.15 kU/L) were independent significant predictors of the degree of tumor reduction achieved during PDS. (4) In the future, MLR, especially in combination with other parameters, may be useful in determining prognosis and selecting the best treatment option (PDS or neoadjuvant chemotherapy + interval debulking surgery) for ovarian cancer patients.

High-grade serous ovarian carcinoma is a unique cancer characterised by universal TP53 mutations and widespread copy number alterations. These copy number alterations include deletion of tumour suppressors and amplification of driver oncogenes. Given their key oncogenic roles, amplified driver genes are often proposed as therapeutic targets. For example, development of anti-HER2 agents has been clinically successful in treatment of ERBB2-amplified tumours. A wide scope of preclinical work has since investigated numerous amplified genes as potential therapeutic targets in high-grade serous ovarian carcinoma. However, variable experimental procedures (e.g., choice of cell lines), ambiguous phenotypes or lack of validation hinders further clinical translation of many targets. In this review, we collate the genes proposed to be amplified therapeutic targets in high-grade serous ovarian carcinoma, and quantitatively appraise the evidence in support of each candidate gene. Forty-four genes are found to have evidence as amplified therapeutic targets; the five highest scoring genes are CCNE1, PAX8, URI1, PRKCI and FAL1. This review generates an up-to-date list of amplified therapeutic target candidates for further development and proposes comprehensive criteria to assist amplified therapeutic target discovery in the future.

Selenium (Se) and manganese (Mn) are essential micronutrients that are important elements of cell metabolism. They are involved in the composition of enzyme systems and regulate enzyme activity. Disturbances in the homeostasis of these micronutrients affect the development of many diseases and carcinogenesis, which can be linked to increased levels of oxidative stress and impaired antioxidant properties of many enzymes. Selenium has a very important function in maintaining immune-endocrine, metabolic and cellular homeostasis. Manganese, on the other hand, is important in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activity. We review the role of selenium and manganese and their effects on tumor growth, metastasis potential and remodeling of the microenvironment. We also describe their role as potential biomarkers in the diagnosis and the potential for the use of Se- and Mn-containing compounds in composition for the treatment of cancer of the reproductive organs.

The fallopian tube (FT) is an important reproductive organ in females. Ample evidence suggests that the distal end of FT is the original site of high-grade serous ovarian carcinoma (HGSC). FT may suffer from repeated injury and repair stimulated by follicular fluid (FF); however, this hypothesis has not been examined. In fact, the molecular mechanism of homeostasis, differentiation, and the transformation of fallopian tube epithelial cells (FTECs) resulting from the stimulation of FF are still enigmatic. In this study, we examined the effects of FF along with factors present in the FF on a variety of FTEC models, including primary cell culture, ALI (air-liquid interface) culture, and 3D organ spheroid culture. We found that FF plays a similar role to estrogen in promoting cell differentiation and organoid formation. Moreover, FF significantly promotes cell proliferation and induces cell injury and apoptosis in high concentrations. These observations may help us to investigate the mechanisms of the initiation of HGSC.

The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic tumor cells, but it also contains supporting stroma, ECM, and soluble molecules. Melanoma cells are continuously in interaction with the components of the microenvironment. In the present review, we focus on the role of the tumor microenvironment components in the modulation of tumor progression and treatment resistance as well as the impact of the tumor microenvironment as a therapeutic target in melanoma.

Cancer is a major burden of disease worldwide and increasing evidence shows that inflammation contributes to cancer development and progression. Eicosanoids are derived from dietary polyunsaturated fatty acids, such as arachidonic acid (AA), and are mainly produced by a series of enzymatic pathways that include cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P-450 epoxygenase (CYP). Eicosanoids consist of at least several hundred individual molecules and play important roles in the inflammatory response and inflammation-related cancers.

Dietary sources of AA and biosynthesis of eicosanoids from AA through different metabolic pathways are summarized. The bioactivities of eicosanoids and their potential molecular mechanisms on inflammation and cancer are revealed. Additionally, current challenges and limitations in eicosanoid research on inflammation-related cancer are discussed.

Dietary AA generates a large variety of eicosanoids, including prostaglandins, thromboxane A2, leukotrienes, cysteinyl leukotrienes, lipoxins, hydroxyeicosatetraenoic acids (HETEs), and epoxyeicosatrienoic acids (EETs). Eicosanoids exert different bioactivities and mechanisms involved in the inflammation and related cancer developments. A deeper understanding of eicosanoid biology may be advantageous in cancer treatment and help to define cellular targets for further therapeutic development.

Ovarian cancer (OC) is one of the deadliest gynecological cancers, largely due to the fast development of metastasis and drug resistance. The immune system is a critical component of the OC tumor microenvironment (TME) and immune cells such as T cells, NK cells, and dendritic cells (DC) play a key role in anti-tumor immunity. However, OC tumor cells are well known for evading immune surveillance by modulating the immune response through various mechanisms. Recruiting immune-suppressive cells such as regulatory T cells (Treg cells), macrophages, or myeloid-derived suppressor cells (MDSC) inhibit the anti-tumor immune response and promote the development and progression of OC. Platelets are also involved in immune evasion by interaction with tumor cells or through the secretion of a variety of growth factors and cytokines to promote tumor growth and angiogenesis. In this review, we discuss the role and contribution of immune cells and platelets in TME. Furthermore, we discuss their potential prognostic significance to help in the early detection of OC and to predict disease outcome.

Sarcopenia is prevalent in ovarian cancer and contributes to poor survival. This study is aimed at investigating the association of prognostic nutritional index (PNI) with muscle loss and survival outcomes in patients with ovarian cancer.

This retrospective study analyzed 650 patients with ovarian cancer treated with primary debulking surgery and adjuvant platinum-based chemotherapy at a tertiary center from 2010 to 2019. PNI-low was defined as a pretreatment PNI of < 47.2. Skeletal muscle index (SMI) was measured on pre- and posttreatment computed tomography (CT) at L3. The cut-off for the SMI loss associated with all-cause mortality was calculated using maximally selected rank statistics.

The median follow-up was 4.2 years, and 226 deaths (34.8%) were observed. With a median duration of 176 days (interquartile range: 166-187) between CT scans, patients experienced an average decrease in SMI of 1.7% (P < 0.001). The cut-off for SMI loss as a predictor of mortality was - 4.2%. PNI-low was independently associated with SMI loss (odds ratio: 1.97, P = 0.001). On multivariable analysis of all-cause mortality, PNI-low and SMI loss were independently associated with all-cause mortality (hazard ratio: 1.43, P = 0.017; hazard ratio: 2.27, P < 0.001, respectively). Patients with both SMI loss and PNI-low (vs. neither) had triple the risk of all-cause mortality (hazard ratio: 3.10, P < 0.001).

PNI is a predictor of muscle loss during treatment for ovarian cancer. PNI and muscle loss are additively associated with poor survival. PNI can help clinicians guide multimodal interventions to preserve muscle and optimize survival outcomes.

Leukocytes are in situ regulators critical for ovarian function. However, little is known about leukocyte subpopulations and their interaction with follicular cells in ovulatory follicles, especially in humans. Single-cell RNA sequencing (scRNA-seq) was performed using follicular aspirates obtained from four IVF patients and identified 13 cell groups: one granulosa cell group, one thecal cell group, 10 subsets of leukocytes, and one group of RBC/platelet. RNA velocity analyses on five granulosa cell populations predicted developmental dynamics denoting two projections of differentiation states. The cell type-specific transcriptomic profiling analyses revealed the presence of a diverse array of leukocyte-derived factors that can directly impact granulosa cell function by activating their receptors (e.g., cytokines and secretory ligands) and are involved in tissue remodeling (e.g., MMPs, ADAMs, ADAMTSs, and TIMPs) and angiogenesis (e.g., VEGFs, PGF, FGF, IGF, and THBS1) in ovulatory follicles. Consistent with the findings from the scRNA-seq data, the leukocyte-specific expression of CD68, IL1B, and MMP9 was verified in follicle tissues collected before and at defined hours after hCG administration from regularly cycling women. Collectively, this study demonstrates that this data can be used as an invaluable resource for identifying important leukocyte-derived factors that promote follicular cell function, thereby facilitating ovulation and luteinization in women.