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BMC Medical Genomics May 2024Ovarian cancer is the most common cause of gynecological cancer death. Pak4 has been proved to be tumorigenic in many types of cancers, but its role in ovarian cancer is...
BACKGROUND
Ovarian cancer is the most common cause of gynecological cancer death. Pak4 has been proved to be tumorigenic in many types of cancers, but its role in ovarian cancer is still not clarified.
METHODS
In this study, we used immunohistochemistry to investigate into Pak4 expression in different histological types of ovarian cancer. TIMER, TISCH2, GEPIA, ualcan, KM plotter, GSCA and GeneMANIA were used to identify the prognostic roles and gene regulation networks of Pak4 in ovarian cancer. Immune infiltration levels were investigated using TIMER database.
RESULTS
Pak4 was highly expressed in ovarian cancers, regardless of different FIGO stages and histological grades. Single cell sequencing database proved that Pak4 was highly expressed in malignant ovarian cancer cells. Pak4 level was significantly correlated with different histological types of ovarian cancer. Pak4 expression was negatively connected with OS and PFS of ovarian cancer patients. Functions of Pak4 and its interacted genes were mainly involved in protein serine/threonine kinase activity, regulation of actin filament-based process and regulation of cytoskeleton organization. Pak4 level was negatively correlated with immune biomarkers of B cell infiltration (p = 2.39e-05), CD8 + T cell infiltration (p = 1.51e-04), neutrophil (p = 1.74e-06) and dendritic cell (p = 4.41e-08). Close correlation was found between Pak4 expression and T cell exhaustion (p < 0.05).
CONCLUSIONS
Our results demonstrated the expression level, gene interaction networks and immune infiltration levels of Pak4 in ovarian cancer. And the results revealed role of Pak4 in tumorigenesis and the possibility to be a potential immunotherapeutic target.
Topics: Humans; p21-Activated Kinases; Female; Ovarian Neoplasms; Gene Expression Regulation, Neoplastic; Prognosis; Carcinogenesis; Biomarkers, Tumor; Lymphocytes, Tumor-Infiltrating; Gene Regulatory Networks
PubMed: 38807162
DOI: 10.1186/s12920-024-01917-4 -
Supportive Care in Cancer : Official... May 2024This study assesses fertility treatment outcomes in female patients who had undergone successful oocyte retrieval following cancer therapy.
PURPOSE
This study assesses fertility treatment outcomes in female patients who had undergone successful oocyte retrieval following cancer therapy.
METHODS
Between January 2020 and December 2022, we collected fertility treatment data from six participating centres in Spain and Germany. All patients associated with this data had undergone successful oocyte retrieval following cancer treatment.
RESULTS
Women had most frequently been diagnosed with a haematological (41.9%), breast (22.6%) or gynaecological malignancy (12.9%); two thirds (67.7%) had previously received a chemotherapy, half a radiotherapy (53.3%) and 45.2% had undergone surgery. On average, 7 years (range 0-28) had passed between cancer treatment and first ovarian stimulation cycle. Forty-nine ovarian stimulation cycles had been conducted on these 31 women between 2004 and 2021 (mean age at first oocyte collection following treatment: 34.8 ± 5.7 years). On average, 7 oocytes were collected per cycle (range 0-26) and 11 were collected per patient (range 0-51). Out of the 190 oocytes collected for immediate use of artificial reproductive technique, 139 were fertilised at a rate of 73%. Live birth rate per fresh transfer was 45% (9/20); no births were reported following cryotransfer (0/10). Mean values of anti-Mullerian hormone (AMH) before stimulation declined with time since treatment; however, oocytes were successfully collected from four women with an AMH of <0.5 ng/ml, although no pregnancies were reported. Ten pregnancies were documented; 3 ended in miscarriage. Two twin and 5 single pregnancies resulted in nine live births. On average, children were carried to term.
CONCLUSION
In this small cohort, oocytes were successfully collected after chemotherapy and radiotherapy, despite-in individual cases-low AMH values. Further studies are needed to enrich the database and ultimately provide appropriate counselling to female cancer patients regarding expectations and ART outcome following cancer therapy.
Topics: Humans; Female; Retrospective Studies; Adult; Oocyte Retrieval; Neoplasms; Spain; Germany; Pregnancy; Fertility Preservation; Ovulation Induction; Oocytes
PubMed: 38806697
DOI: 10.1007/s00520-024-08586-0 -
Journal of Ovarian Research May 2024The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS),...
BACKGROUND
The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS), especially in patients with diminished ovarian reserve (DOR). During in vitro fertilization-embryo transfer (IVF-ET) treatment, luteal phase estrogen pretreatment may enhance follicular development synchronization and yield of mature oocytes. However, the effect of estrogen pretreatment in DOR patients with elevated basal follicle-stimulating hormone (FSH) levels has not been well studied.
METHODS
We retrospectively analyzed the clinical data of patients with elevated basal FSH levels and DOR (401 cycles) who underwent IVF/intracytoplasmic monosperm injection (ICSI)-assisted conception. Both groups were treated with a flexible gonadotropin-releasing hormone (GnRH) antagonist regimen and were further divided into two groups according to whether they received luteal estrogen pretreatment. There were 79 patients in the estrogen pretreatment group and 322 patients in the control group. On the second day of the menstrual cycle, gonadotropin (Gn) stimulation of the ovaries was initiated. The general characteristics, clinical, biological parameters and outcomes of the two groups were compared.
RESULTS
The basic profiles of the two groups were similar (P > 0.05). More patients in the pretreatment group showed FSH rebound after gonadotropin (Gn) initiation, resulting in a significantly higher number of Gn days and total Gn than those in the control group (P < 0.05). There was no statistically significant difference in the number of days of antagonist use, follicle output rate (FORT), number of metaphase II(MII)eggs obtained, number of Two pronuclei (2PN) fertilized, number of D quality embryos, blastocyst formation rate, fresh embryo clinical pregnancy rate, cumulative pregnancy rate, and non-transferable embryo rate between the two groups (P > 0.05).
CONCLUSIONS
The use of luteal phase estrogen pretreatment in patients with elevated basal FSH combined with DOR resulted in high FSH levels after the release of negative feedback, which was detrimental to early follicular growth, did not increase the follicular output rate, may have increased the use and duration of controlled ovarian stimulation drugs, and did not increase the number of eggs gained or improve clinical outcomes.
Topics: Humans; Female; Retrospective Studies; Adult; Follicle Stimulating Hormone; Ovulation Induction; Ovarian Reserve; Estrogens; Fertilization in Vitro; Pregnancy; Gonadotropin-Releasing Hormone; Pregnancy Rate; Embryo Transfer
PubMed: 38802887
DOI: 10.1186/s13048-024-01415-2 -
Cancer Medicine May 2024Numerous observational studies have investigated the potential link between hypertensive disorders of pregnancy (HDPs) and the subsequent risks of gynecologic tumors,...
BACKGROUND
Numerous observational studies have investigated the potential link between hypertensive disorders of pregnancy (HDPs) and the subsequent risks of gynecologic tumors, yet the findings have been inconsistent. In this study, we utilized Mendelian randomization (MR) approach to assess the influence of HDPs on the future risks of ovarian, cervical, endometrial, and breast cancer and uterine fibroids, controlling for confounding factors.
METHODS
The genome-wide association studies (GWAS) summary data relevant to HDPs was obtained from the FinnGen databases (10,736 cases and 136,325 controls). Gynecologic tumor outcomes were extracted from the IEU Open GWAS project and UK Biobank (47,690 cases and 1, 092,073 controls). The inverse variance weighted (IVW) approach was selected as the principal method for MR analysis, supplemented by MR-Egger, weighted median, weighted model, simple model methods, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out method. Multivariate MR (MVMR) analysis was conducted after adjusting systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes mellitus (T2DM).
RESULTS
Our univariate MR analysis (UVMR) results revealed no significant relationship between HDPs and the risks of ovarian cancer (odds ratio [OR] = 0.924, p = 0.360), cervical cancer (OR = 1.230, p = 0.738), endometrial cancer (OR = 1.006, p = 0.949), uterine fibroids (OR = 1.155, p = 0.158), and breast cancer (OR = 0.792, p = 0.241) by IVW test. Similar results were observed in gestational hypertension and preeclampsia/eclampsia. Additionally, our study detected neither heterogeneity nor pleiotropy. MVMR analysis also provided no evidence of a causal association between HDPs and common gynecologic tumors after adjusting SBP, BMI, and T2DM.
CONCLUSION
We discovered no causal relationship between HDPs and ovarian, cervical, endometrial, breast cancer, and uterine fibroids in European populations. However, present analysis did not explore the effect of HDPs on the subtypes of gynecologic tumors across varied ethnic populations, which may require additional research.
Topics: Humans; Female; Mendelian Randomization Analysis; Pregnancy; Genome-Wide Association Study; Genital Neoplasms, Female; Hypertension, Pregnancy-Induced; Risk Factors; Polymorphism, Single Nucleotide
PubMed: 38800978
DOI: 10.1002/cam4.7300 -
Cureus May 2024Background Polycystic ovarian syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. It is characterized by dyslipidemia, hormonal...
Background Polycystic ovarian syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. It is characterized by dyslipidemia, hormonal imbalances, and metabolic dysfunctions. Vitamin D deficiency may be implicated in the pathogenesis of PCOS, potentially exacerbating its metabolic syndrome. However, the exact interplay between these factors remains underexplored. Aim This study aimed to evaluate serum levels of vitamin D and its association with modalities of PCOS among women with PCOS and healthy controls. Methods This was a hospital-based case-control study where 60 women newly diagnosed with PCOS and 56 non-PCOS controls were consecutively recruited within a 10-month period. The women aged 20-40 were recruited at the gynecology clinics of Lagos State University Teaching Hospital and Lagos Island Maternity Hospital. PCOS was diagnosed using the Rotterdam's criteria. The biodata, anthropometry, clinical features, serum vitamin D, cortisol, progesterone, testosterone, estradiol, prolactin, anti-Mullerian hormone (AMH), thyroid-stimulating hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), insulin, fasting blood glucose (FBG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and very-low-density lipoprotein cholesterol (VLDL-C) levels of PCOS-diagnosed women were assessed and compared with those of women without PCOS. The exclusion criteria comprised known diabetics, women with gynecological pathologies such as fibroids, and women on medications affecting the study analytes or hormones. Statistical analyses included chi-square or Fisher's exact tests for categorical variables, student t-test for continuous variables, and Pearson's correlation for assessing relationships between continuous variables. The significance level was set at p<0.05 and a confidence interval of 95%. Results Individuals with PCOS exhibited a younger mean age (26.90±3.73 versus 29.95±5.00 years, p=0.001) and a higher prevalence of irregular menstrual patterns (46.7% versus 14.3%, p=0.0001) and acne (58.3% versus 37.5%, p=0.025). Moreover, PCOS was associated with elevated levels of TC (p = 0.03), TG (p = 0.03), LDL-C (p = 0.014), FBG (p = 0.001), LH:FSH ratio (p = 0.002), AMH (p = 0.0001), and testosterone (p = 0.003), but low progesterone (p = 0.001) and vitamin D (p = 0.033), alongside a higher incidence of vitamin D deficiency (33.3% versus 26.1%) and insufficiency (66.7% versus 56.5%). Additionally, significant but weak correlations were observed between serum vitamin D levels and waist-hip ratio (r = 0.4, p = 0.016) and FBG (r = -0.4, p = 0.036) in the PCOS group, suggesting potential metabolic implications. Conclusion The PCOS subjects in this study had decreased vitamin D and progesterone levels, with elevated concentrations of testosterone, AMH, lipid profile (TC, LDL, and TG), FBG, and LH:FSH ratio. Studies on the therapeutic effect of vitamin D administration in managing PCOS will need to be further evaluated.
PubMed: 38800769
DOI: 10.7759/cureus.60975 -
Frontiers in Endocrinology 2024Currently, three crucial questions regarding the reliability of ovarian reserve measures in women with ovarian endometrioma during the reproductive age are being... (Review)
Review
The impact of ovarian endometrioma and endometriotic cystectomy on anti-Müllerian hormone, and antral follicle count: a contemporary critical appraisal of systematic reviews.
Currently, three crucial questions regarding the reliability of ovarian reserve measures in women with ovarian endometrioma during the reproductive age are being discussed. Firstly, the effects of endometriotic cystectomy on short and long-term ovarian reserve. Secondly, the accuracy of serum anti-Müllerian hormone (AMH) and antral follicle count (AFC) in estimating ovarian reserve in these cases. Thirdly, the impact of endometrioma itself on the ovarian reserve over time in such cases. The purpose of the present review is to critically assess available systematic reviews and meta-analyses that have explored these questions. Nine eligible reviews were found following a systematic search on PubMed.com and similarly assessed. These reviews varied considerably regarding the level of evidence, as per an identical comprehensive scoring system. Moderate to high-quality evidence demonstrates that endometriotic cystectomy, by the stripping technique, adversely affects ovarian reserve in the short and long term, up to 9-18 months post-surgery. Damage to ovarian reserve was considerable but more pronounced in bilateral cases than unilateral cases, equivalent to 39.5% and 57.0%, respectively. Repeat endometriotic cystectomy is detrimental to ovarian reserve. The impact of endometrioma diameter on ovarian reserve before or after surgery is still unclear. Moderate to high-quality evidence, relying on simultaneous assessment of both ovarian reserve measures, shows that AMH is sensitive while AFC is not in cases undergoing ovarian cystectomy. AMH should be the biomarker of choice for counseling and managing women with endometrioma in their reproductive age, especially before surgery. While there is some evidence to show that endometrioma per se may harm ovarian reserve, this evidence is not robust, and there is good-quality evidence to challenge this notion. It is necessary to conduct further targeted RCTs, systematic reviews, and meta-analyses based on solid methodological grounds to increase the level of evidence, refine quantitative estimates, investigate open questions, and decrease heterogeneity.
Topics: Humans; Female; Endometriosis; Anti-Mullerian Hormone; Ovarian Reserve; Ovarian Follicle; Ovarian Diseases; Systematic Reviews as Topic
PubMed: 38800489
DOI: 10.3389/fendo.2024.1397279 -
IScience Jun 2024We have purified Peptidase M84 from in an effort to isolate anticancer proteases from environmental microbial isolates. This metallo-protease had no discernible impact...
We have purified Peptidase M84 from in an effort to isolate anticancer proteases from environmental microbial isolates. This metallo-protease had no discernible impact on normal cell survival, but it specifically induced apoptosis in ovarian cancer cells. PAR-1, a GPCR which is reported to be overexpressed in ovarian cancer cells, was identified as a target of Peptidase M84. We observed that Peptidase M84 induced PAR-1 overexpression along with activating its downstream signaling effectors NF-κB and MAPK to promote excessive reactive oxygen species (ROS) generation. This evoked apoptotic death of the ovarian cancer cells through the intrinsic route. In set-up, weekly intraperitoneal administration of Peptidase M84 in syngeneic mice significantly diminished ascites accumulation, increasing murine survival rates by 60%. Collectively, our findings suggested that Peptidase M84 triggered PAR-1-mediated oxidative stress to act as an apoptosis inducer. This established Peptidase M84 as a drug candidate for receptor mediated targeted-therapy of ovarian cancer.
PubMed: 38799586
DOI: 10.1016/j.isci.2024.109828 -
IScience Jun 2024Germline pathogenic variants in and (gpath(/)) represent genetic susceptibility for hereditary breast and ovarian cancer syndrome. Tumor-immune interactions are key...
Germline pathogenic variants in and (gpath(/)) represent genetic susceptibility for hereditary breast and ovarian cancer syndrome. Tumor-immune interactions are key contributors to breast cancer pathogenesis. Although earlier studies confirmed pro-tumorigenic immunological alterations in breast cancer patients, data are lacking in healthy carriers of gpath(/). Peripheral blood mononuclear cells of 66 women with or without germline predisposition or breast cancer were studied with a mass cytometry panel that identified 4 immune subpopulations of altered frequencies between healthy controls and healthy gpath() carriers, while no difference was observed in healthy gpath() carriers compared to controls. Moreover, 3 (one IgD-CD27CD95 B cell subpopulation and two CD45RA-CCR7+CD38 CD4 T cell subpopulations) out of these 4 subpopulations were also elevated in triple-negative breast cancer patients compared to controls. Our results reveal an activated peripheral immune phenotype in healthy carriers of gpath() that needs to be further elucidated to be leveraged in risk-reducing strategies.
PubMed: 38799565
DOI: 10.1016/j.isci.2024.109882 -
Viruses May 2024Duck Tembusu Virus (DTMUV) is a pathogen of the Flaviviridae family that causes infections in poultry, leading to significant economic losses in the duck farming... (Review)
Review
Duck Tembusu Virus (DTMUV) is a pathogen of the Flaviviridae family that causes infections in poultry, leading to significant economic losses in the duck farming industry in recent years. Ducks infected with this virus exhibit clinical symptoms such as decreased egg production and neurological disorders, along with serious consequences such as ovarian hemorrhage, organ enlargement, and necrosis. Variations in morbidity and mortality rates exist across different age groups of ducks. It is worth noting that DTMUV is not limited to ducks alone; it can also spread to other poultry such as chickens and geese, and antibodies related to DTMUV have even been found in duck farm workers, suggesting a potential risk of zoonotic transmission. This article provides a detailed overview of DTMUV research, delving into its genomic characteristics, vaccines, and the interplay with host immune responses. These in-depth research findings contribute to a more comprehensive understanding of the virus's transmission mechanism and pathogenic process, offering crucial scientific support for epidemic prevention and control.
Topics: Animals; Ducks; Flavivirus; Flavivirus Infections; Genome, Viral; Poultry Diseases; Viral Vaccines; Farmers; Antibodies, Viral; Humans
PubMed: 38793692
DOI: 10.3390/v16050811 -
Journal of Clinical Medicine May 2024Solid pseudopapillary neoplasms (SPNs) are rare and mainly originate from the pancreas. SPNs originating from the ovary (SPN-O) are extremely rare, and only 13 cases...
INTRODUCTION
Solid pseudopapillary neoplasms (SPNs) are rare and mainly originate from the pancreas. SPNs originating from the ovary (SPN-O) are extremely rare, and only 13 cases have been reported in the English literature since 2010.
CASE
We report a 31-year-old woman with SPN-O accompanied by multiple metastases in the abdominal cavity. The patient underwent staging surgery and cytoreduction. Furthermore, the multidisciplinary board decided on adjuvant chemotherapy with an FP regimen (fluorouracil plus cisplatin) because a microscopic metastasis was discovered in the peritoneum near the appendix. Next-generation sequencing showed some pathologic mutations of oncogenes/cancer-associated genes, including and . This is the fourteenth case of SPN-O and the first one to demonstrate the pathogenic mutant variant in SPN-O. The patient showed 8 months of disease-free survival until February 2024.
CONCLUSION
The combination of R0 cytoreduction with FOLFIRI chemotherapy appears to be an effective and feasible treatment option.
PubMed: 38792331
DOI: 10.3390/jcm13102791