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Medicine Jul 2023To explore the association between serum lipids and the occurrence and development of endometriosis using a retrospective review of clinical data. A total of 177...
To explore the association between serum lipids and the occurrence and development of endometriosis using a retrospective review of clinical data. A total of 177 patients who underwent laparoscopic or open surgery due to benign ovarian masses, 117 patients with endometriosis (53 stage III and 64 stage IV), and 60 patients with benign ovarian masses without endometriosis were selected from the gynecology department of Maternal and Child Health Hospital of Hubei Province, between January 1, 2020, and October 30, 2022, to search for endometriosis occurrence by retrospectively analyzed the patients clinical data Risk factors for development and to explore the relationship between blood lipids and endometriosis. The scores of estradiol (E2), carbohydrate antigen 125 (CA125), and pain in the endo - and non-endometriosis groups were significantly different (P < .05), but there was no significant correlation between these 3. There were significant differences (P < .05) in E2, triglyceride (TG), CA125, and the size of the masses between patients with stage III and IV endometriosis. TG, E2, and CA125 were found to be valuable as separate indicators for the prediction of endometriosis, and the 3 indicators could improve the accuracy of the diagnosis of endometriosis when combined. Triglycerides may be positively correlated with the severity of endometriosis. The combination of TG, E2 and CA125 can improve the accuracy of the diagnosis of endometriosis staging.
Topics: Female; Child; Humans; Retrospective Studies; Endometriosis; CA-125 Antigen; Estrogens; Ovarian Neoplasms; Biomarkers, Tumor
PubMed: 37478235
DOI: 10.1097/MD.0000000000034348 -
Cancers Aug 2023Ovarian tissue cryopreservation and transplantation are the only available fertility techniques for prepubertal girls with cancer. Though autotransplantation carries a... (Review)
Review
BACKGROUND
Ovarian tissue cryopreservation and transplantation are the only available fertility techniques for prepubertal girls with cancer. Though autotransplantation carries a risk of reintroducing malignant cells, it can be avoided by identifying minimal infiltrative disease (MID) within ovarian tissue.
METHODS
A broad search for peer-reviewed articles in the PubMed database was conducted in accordance with PRISMA guidelines up to March 2023. Search terms included 'minimal residual disease', 'cryopreservation', 'ovarian', 'cancer' and synonyms.
RESULTS
Out of 542 identified records, 17 were included. Ovarian tissues of at least 115 girls were evaluated and categorized as: hematological malignancies ( = 56; 48.7%), solid tumors ( = 42; 36.5%) and tumors of the central nervous system ( = 17; 14.8%). In ovarian tissue of 25 patients (21.7%), MID was detected using RT-qPCR, FISH or multicolor flow cytometry: 16 of them (64%) being ALL ( rearrangements with/without , , , fusion transcripts), 3 (12%) Ewing sarcoma ( fusion transcript, rearrangements), 3 (12%) CML ( fusion transcript, ) and 3 (12%) AML (leukemia-associated immunophenotypes, fusion transcript) patients.
CONCLUSION
While the majority of malignancies were found to have a low risk of containing malignant cells in ovarian tissue, further studies are needed to ensure safe implementation of future fertility restoration in clinical practice.
PubMed: 37686475
DOI: 10.3390/cancers15174199 -
Journal of Translational Medicine Sep 2023Ovarian cancer (OC) is a highly aggressive gynecological malignancy prevalent worldwide. Most OC cases are typically diagnosed at advanced stages, which has led to a...
BACKGROUND
Ovarian cancer (OC) is a highly aggressive gynecological malignancy prevalent worldwide. Most OC cases are typically diagnosed at advanced stages, which has led to a 5-year overall survival rate of less than 35% following conventional treatment. Furthermore, immune checkpoint inhibitor therapy has shown limited efficacy in the treatment of patients with OC, and CAR-T therapy has also demonstrated modest results owing to inadequate T cell infiltration. Therefore, novel strategies must be developed to enhance T cell persistence and trafficking within the OC tumor microenvironment.
METHODS
In this study, we developed a novel adoptive T-cell therapy for ovarian cancer based on a chimeric antigen receptor structure. We used a ligand-receptor binding motif to enhance the therapeutic effect of targeting CA125. Since mesothelin can naturally bind to CA125 with high affinity, we concatenated the core-binding fragment of mesothelin with the 4-1BB and CD3ζ signal fragments to assemble a novel CA125-targeting chimeric receptor (CR). The CAR structure targeting CA125 derived from the 4H11 antibody was also constructed. CR- and CAR-encoding RNA were electroporated into T cells to evaluate their antitumor activity both in vitro and in vivo.
RESULTS
While CR-T or CAR-T cells exhibited moderate activity against two ovarian cancer cell lines, T cells co-expressing CR and CAR exhibited a superior killing effect compared to T cells expressing either CR or CAR alone. Furthermore, upon interaction with ovarian tumors, the ability of CR and CAR T cells to release activation markers and functional cytokines increased significantly. Similarly, CR and CAR co-expressing T cells persistently controlled the growth of transplanted ovarian cancer tumors in NSG mice and significantly prolonged the overall survival of tumor-challenged mice. Transcriptome sequencing revealed that the survival and cytotoxicity of T cells co-expressing CR and CAR were significantly altered compared with those of T cells expressing either CR or CAR.
CONCLUSION
Our findings demonstrate that CA125 targeting CR and CAR can synergistically kill ovarian cancer cells, indicating that CA125 targeting by the two binding motifs simultaneously in tumors may improve the therapeutic outcomes of ovarian cancer treatment.
Topics: Animals; Mice; Female; Humans; Mesothelin; Ligands; T-Lymphocytes; Ovarian Neoplasms; CA-125 Antigen; Receptors, Chimeric Antigen; Tumor Microenvironment
PubMed: 37670338
DOI: 10.1186/s12967-023-04271-8 -
Journal of Ovarian Research Sep 2023Tumor-associated lncRNAs regulated by epigenetic modification switches mediate immune escape and chemoresistance in ovarian cancer (OC). However, the underlying...
Tumor-associated lncRNAs regulated by epigenetic modification switches mediate immune escape and chemoresistance in ovarian cancer (OC). However, the underlying mechanisms and concrete targets have not been systematically elucidated. Here, we discovered that methylation modifications played a significant role in regulating immune cell infiltration and sensitizing OC to chemotherapy by modulating immune-related lncRNAs (irlncRNAs), which represent tumor immune status. Through deep analysis of the TCGA database, a prognostic risk model incorporating four methylation-related lncRNAs (mrlncRNAs) and irlncRNAs was constructed. Twenty-one mrlncRNA/irlncRNA pairs were identified that were significantly related to the overall survival (OS) of OC patients. Subsequently, we selected four lncRNAs to construct a risk signature predictive of OS and indicative of OC immune infiltration, and verified the robustness of the risk signature in an internal validation set. The risk score was an independent prognostic factor for OC prognosis, which was demonstrated via multifactorial Cox regression analysis and nomogram. Moreover, risk scores were negatively related to the expression of CD274, CTLA4, ICOS, LAG3, PDCD1, and PDCD1LG2 and negatively correlated with CD8, CD4, and Treg tumor-infiltrating immune cells. In addition, a high-risk score was associated with a higher IC50 value for cisplatin, which was associated with a significantly worse clinical outcome. Next, a competing endogenous RNA (ceRNA) network and a signaling pathway controlling the infiltration of CD8 T cells were explored based on the lncRNA model, which suggested a potential therapeutic target for immunotherapy. Overall, this study constructed a prognostic model by pairing mrlncRNAs and irlncRNAs and revealed the critical role of the FTO/RP5-991G20.1/hsa-miR-1976/MEIS1 signaling pathway in regulating immune function and enhancing anticancer therapy.
Topics: Humans; Female; Methylation; RNA, Long Noncoding; CD8-Positive T-Lymphocytes; Drug Resistance, Neoplasm; Ovarian Neoplasms; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 37674251
DOI: 10.1186/s13048-023-01260-9 -
Journal For Immunotherapy of Cancer Dec 2023Antibody therapies can direct natural killer (NK) cells to tumor cells, tumor-associated cells, and suppressive immune cells to mediate antibody-dependent cell-mediated...
BACKGROUND
Antibody therapies can direct natural killer (NK) cells to tumor cells, tumor-associated cells, and suppressive immune cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). This antigen-specific effector function of human NK cells is mediated by the IgG Fc receptor CD16A (FcγRIIIA). Preclinical and clinical studies indicate that increasing the binding affinity and avidity of CD16A for antibodies improves the therapeutic potential of ADCC. CD64 (FcγRI), expressed by myeloid cells but not NK cells, is the only high affinity IgG Fc receptor and is uniquely capable of stably binding to free monomeric IgG as a physiological function. We have reported on the generation of the FcγR fusion CD64/16A, consisting of the extracellular region of CD64 and the transmembrane and cytoplasmic regions from CD16A, retaining its signaling and cellular activity. Here, we generated induced pluripotent stem cell (iPSC)-derived NK (iNK) cells expressing CD64/16A as a potential adoptive NK cell therapy for increased ADCC potency.
METHODS
iPSCs were engineered to express CD64/16A as well as an interleukin (IL)-15/IL-15Rα fusion (IL-15RF) protein and differentiated into iNK cells. iNK cells and peripheral blood NK cells were expanded using irradiated K562-mbIL21-41BBL feeder cells and examined. NK cells, ovarian tumor cell lines, and therapeutic monoclonal antibodies were used to assess ADCC in vitro, performed by a DELFIA EuTDA assay or in real-time by IncuCyte assays, and in vivo. For the latter, we developed a xenograft mouse model with high circulating levels of human IgG for more physiological relevance.
RESULTS
We demonstrate that (1) iNK-CD64/16A cells after expansion or thaw from cryopreservation can be coupled to therapeutic antibodies, creating armed iNK cells; (2) antibody-armed iNK-CD64/16A cells can be redirected by added antibodies to target new tumor antigens, highlighting additional potential of these cells; (3) cytokine-autonomous activity by iNK-CD64/16A cells engineered to express IL-15RF; and that (4) antibody-armed iNK-CD64/16A cells thawed from cryopreservation are capable of sustained and robust ADCC in vitro and in vivo, as determined by using a modified tumor xenograft model with high levels of competing human IgG.
CONCLUSIONS
iNK cells expressing CD64/16A provide an off-the-shelf multiantigen targeting platform to address tumor heterogeneity and mitigate antigen escape.
Topics: Humans; Animals; Mice; Receptors, IgG; Induced Pluripotent Stem Cells; Killer Cells, Natural; Cell Line, Tumor; Immunoglobulin G
PubMed: 38056893
DOI: 10.1136/jitc-2023-007280 -
Gynecological Endocrinology : the... Dec 2023Though recent studies have pointed out different manifestations between obese and nonobese patients with polycystic ovarian syndrome (PCOS), there is no clear evidence... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Though recent studies have pointed out different manifestations between obese and nonobese patients with polycystic ovarian syndrome (PCOS), there is no clear evidence to confirm this viewpoint. Therefore, the metabolic characteristics of obese and nonobese patients with PCOS were systematically compared through meta-analysis in this study.
METHODS
Data were searched from PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wanfang databases. Articles on obese and nonobese patients with PCOS published from database inception to January 2022 were included. Meta-analysis was performed using Stata 16.0 statistical software.
RESULTS
A total of 739 articles were initially retrieved, and ultimately 14 studies were involved in the meta-analysis. Specifically, there were 801 patients in the observation group (obese patients with PCOS) and 925 patients in the control group (nonobese patients with PCOS). Compared with the control group, the observation group had significantly lower levels of sex hormone-binding globulin (SHBG), high-density lipoprotein (HDL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and higher levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL). Nevertheless, there were no significant differences between the two groups in systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, and testosterone.
CONCLUSION
Compared with nonobese patients with PCOS, obese patients with PCOS have worse blood lipid parameters and lower levels of LH and FSH. Also, there are significant differences in metabolic characteristics between the two groups of patients. Most importantly, our findings provide guidance for the clinical diagnosis and treatment of PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Luteinizing Hormone; Obesity; Follicle Stimulating Hormone; Triglycerides; Testosterone
PubMed: 37524309
DOI: 10.1080/09513590.2023.2239934 -
BMC Medical Genomics Sep 2023The most prevalent mutation in ovarian cancer is the TP53 mutation, which impacts the development and prognosis of the disease. We looked at how the TP53 mutation...
BACKGROUND
The most prevalent mutation in ovarian cancer is the TP53 mutation, which impacts the development and prognosis of the disease. We looked at how the TP53 mutation associates the immunophenotype of ovarian cancer and the prognosis of the disease.
METHODS
We investigated the state of TP53 mutations and expression profiles in culturally diverse groups and datasets and developed an immune infiltration predictive model relying on immune-associated genes differently expressed between TP53 WT and TP53 MUT ovarian cancer cases. We aimed to construct an immune infiltration predictive model (IPM) to enhance the prognosis of ovarian cancer and investigate the impact of the IPM on the immunological microenvironment.
RESULTS
TP53 mutagenesis affected the expression of seventy-seven immune response-associated genes. An IPM was implemented and evaluated on ovarian cancer patients to distinguish individuals with low- and high-IPM subgroups of poor survival. For diagnostic and therapeutic use, a nomogram is thus created. According to pathway enrichment analysis, the pathways of the human immune response and immune function abnormalities were the most associated functions and pathways with the IPM genes. Furthermore, patients in the high-risk group showed low proportions of macrophages M1, activated NK cells, CD8 T cells, and higher CTLA-4, PD-1, PD-L1, and TIM-3 than patients in the low-risk group.
CONCLUSIONS
The IPM model may identify high-risk patients and integrate other clinical parameters to predict their overall survival, suggesting it is a potential methodology for optimizing ovarian cancer prognosis.
Topics: Humans; Female; CD8-Positive T-Lymphocytes; Ovarian Neoplasms; Mutation; Killer Cells, Natural; Macrophages; Tumor Microenvironment
PubMed: 37759229
DOI: 10.1186/s12920-023-01657-x -
Pakistan Journal of Medical Sciences 2023To study the correlation of Triclosan (TCS) exposure with typing and staging of endometriosis, and with other potential influencing factors.
OBJECTIVE
To study the correlation of Triclosan (TCS) exposure with typing and staging of endometriosis, and with other potential influencing factors.
METHODS
This was a retrospective study. Thirty two patients that were diagnosed with endometriosis by laparoscopy or surgery in Taicang First People's Hospital from May 2020 to December 2021 were enrolled in the endometriosis group, and patients who were confirmed free of endometriosis by surgeries for other purposes during the same period were enrolled as the control group. All blood samples were tested twice in two different vials. The association of TCS exposure level with occurrence, staging, typing of endometriosis, and income of the patients were analyzed.
RESULTS
Patients with endometriosis had significantly higher TCS exposure levels than the control group. TCS exposure level in patients with endometriosis was positively correlated with patient income), and was significantly higher in patients with Stage-IV endometriosis than in those with Stage-III and II diseases. TCS exposure levels showed no significant difference among patients with ovarian type, ovarian + peritoneal type, and deep nodular type endometriosis TCS exposure level in patients with endometriosis was positively correlated with the staging of the disease. TCS exposure was highly positively correlated with the staging of the disease in patients with ovarian type endometriosis and in patients with deep nodular endometriosis, but there's no such correlation in patients with ovarian + peritoneal type endometriosis.
CONCLUSION
TCS exposure level in endometriosis patients was higher than that in normal women, and is positively correlated with endometriosis staging and income of the patients.
PubMed: 37936784
DOI: 10.12669/pjms.39.6.7170 -
Frontiers in Endocrinology 2023To evaluate the effects of ovarian injection of autologous platelet rich plasma (aPRP) on patients with poor ovarian responder (POR) based on the existing clinical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effects of ovarian injection of autologous platelet rich plasma (aPRP) on patients with poor ovarian responder (POR) based on the existing clinical evidence.
METHODS
According to systematic review and meta-analysis, we comprehensively searched nine databases established as of September 6, 2023, and evaluated the impact of ovarian PRP infusion on poor ovarian responder. The research results include serum follicle-stimulating hormone(FSH) and anti-Mullerian hormone(AMH) levels, antral Follicle Count(AFC), oocyte number, and embryo number. The Newcastle Ottawa Scale (NOS) was used to evaluate the quality of inclusion in trials.
RESULTS
Add up to 10 studies consisting of 793 participants were included in the meta-analysis. A review of existing evidence showed that intraovarian injection of PRP has significant therapeutic effects in increasing levels of anti-Müllerian hormone (AMH) (SMD=0.44,95% CI [0.07,0.81], p=0.02), antral follicle count (AFC) (MD=1.15,95% CI [0.4,1.90], p=0.003), oocyte count (MD=0.91, 95% CI [0.40, 1.41], p=0.0004), and embryo number (MD=0.78, 95% CI [0.5,1.07], p<0.0001). We compared the relevant data of patients before and after treatment after 2 months of intervention. It can be seen that ovarian injection of PRP treatment for 2 months has better effects in reducing FSH levels, increasing AMH levels, increasing antral follicle count, and increasing the number of oocytes and embryos (p<0.05). When the dose of PRP injected into each ovary was ≥ 4ml, there was also a significant correlation (p<0.05) with improving the number of AFC, oocytes and embryos. Significant heterogeneity existed among the studies.
CONCLUSION
The pooled results suggest that intra-ovarian injection of PRP can promote ovarian regeneration and improve the reproductive outcomes of patients with ovarian dysfunction. This therapy may have significant clinical potential in improving sex hormone levels, increasing AFC, oocyte count, and embryo count. However, this findings still requires more rigorous and extensive trials worldwide to determine the value of intra-ovarian injection of PRP in POR patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk, Identifier CRD42023451232.
Topics: Female; Humans; Ovary; Fertilization in Vitro; Anti-Mullerian Hormone; Ovulation Induction; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Platelet-Rich Plasma
PubMed: 38155954
DOI: 10.3389/fendo.2023.1292168 -
Cancer Causes & Control : CCC Jan 2024Five-year relative survival for ovarian cancer remains below 50%. Strategies to improve outcomes are needed. Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations...
PURPOSE
Five-year relative survival for ovarian cancer remains below 50%. Strategies to improve outcomes are needed. Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations [measure of vitamin D status] at and before diagnosis have been associated with longer survival in cancer patients; however, data for ovarian cancer are limited. We aimed to determine if 25(OH)D concentrations during and after primary treatment were associated with ovarian cancer-specific survival.
METHODS
We used data from a nationwide prospective cohort study of women with ovarian cancer. Among 886 participants treated with chemotherapy, 700 (79%) had a blood sample collected during (n = 591) and/or after (n = 458) primary treatment. These were tested for 25(OH)D. Clinical and survival data were abstracted from medical records. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between 25(OH)D and ovarian cancer-specific survival.
RESULTS
Mean 25(OH)D concentrations were lower during than after primary treatment (82 and 91 nmol/L, respectively); only 14% and 8% had concentrations below 50 nmol/L during and after primary treatment, respectively. There was no association between 25(OH)D and ovarian cancer-specific survival during five years of follow-up [HR 1.10 (95% CI: 0.76, 1.61) and 0.95 (0.54, 1.68) for the highest vs. lowest quintile during and after treatment, respectively].
CONCLUSIONS
We did not observe any association between serum 25(OH)D concentration and ovarian cancer-specific survival. Our results suggest that, in the absence of vitamin D deficiency, vitamin D supplementation to improve ovarian cancer survival is not warranted.
Topics: Humans; Female; Prospective Studies; Vitamin D; Vitamin D Deficiency; Vitamins; Ovarian Neoplasms
PubMed: 37526780
DOI: 10.1007/s10552-023-01757-0