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1.
Biol Reprod ; 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39303127

ABSTRACT

Recurrent miscarriage (RM) is a chronic and heterogeneous pregnancy disorder lacking effective treatment. Alterations at the maternal-fetal interface are commonly observed in RM, with the loss of certain cell subpopulations believed to be a key cause. Through single-cell sequencing of RM patients and healthy donors, we aim to identify aberrancy of cellular features in RM tissues, providing new insights into the research. Natural killer (NK) cells, the most abundant immune cells in the decidua, are traditionally classified into dNK1, dNK2, and dNK3. In this study, we identified a new subset, dNK1/2, absent in RM tissues. This subset was named because it expresses biomarkers of both dNK1 and dNK2. With further analysis, we discovered that dNK1/2 cells play roles in immunoregulation and cytokine secretion. On the villous side of the interface, a notable decrease of extravillous trophoblast (EVT) cells was identified in RM tissues. We clustered EVTs into EVT1 (absent in RM) and EVT2 (retained in RM). Pseudotime analysis revealed distinct differentiation paths, identifying CCNB1, HMGB1, and NPM1 as EVT1 biomarkers. Additionally, we found that EVT1 is involved in the regulation of cell death, while EVT2 exhibited more angiogenic activity. Cell communication analysis revealed that interaction between EVT1 and dNK1/2 mediates chemotaxis and endothelial cell regulation, crucial for spiral artery remodeling. The loss of this interaction may impair decidualization, which is associated with RM. In summary, we propose that the loss of dNK1/2 and EVT1 cells is a significant pathological feature of RM.

2.
Article in English | MEDLINE | ID: mdl-39258484

ABSTRACT

OBJECTIVE: The aim of this study was to identify survival rates and potential prognostic factors of ovarian squamous cell carcinoma (OSCC), offering valuable insights for clinical decision making. METHODS: Leveraging the Surveillance, Epidemiology, and End Results (SEER) database, we selected 11 078 serous carcinoma (SC) patients and 198 OSCC patients based on predetermined criteria diagnosed from 2000 to 2020. We compared the overall survival (OS) and cancer-specific survival (CSS) before and after propensity score matching (PSM) in two groups. Prognostic differences were also compared between OSCC and SC groups at different stages. Univariate and multivariate Cox regression analyses were performed to investigate the impact of clinical and pathologic variables on the survival of patients with OSCC. Finally, we developed and validated a nomogram predictive model. RESULTS: OSCC tumors exhibited distinct characteristics, being relatively larger, more frequently unilateral, and better differentiated than SC tumors. After PSM, Kaplan-Meier analysis revealed significantly lower survival rates for OSCC patients in Stages IIB-IV, while Stages IA-IC displayed comparable survival. Independent risk factors for OSCC patients included advanced age, single marital status, higher tumor stage, and increased tumor size. Conversely, higher median household income and chemotherapy emerged as independent protective factors. Our predictive model and nomogram accurately forecasted patient survival rates in both SEER and internal validation datasets. CONCLUSION: OSCC patients face significantly poorer prognosis than their SC counterparts, except in the very early stages. Higher median household income was associated with better OSCC survival.

3.
Jpn J Radiol ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39254904

ABSTRACT

OBJECTIVES: This study aimed to identify the magnetic resonance imaging (MRI)-based radiomics phenotypes of intermediate-to-high-risk endometrial cancers (ECs), explore their association with histopathologic features, and compare their prognostic ability with the International Federation of Gynecology and Obstetrics (FIGO) stage. METHODS: This study retrospectively recruited 355 patients with pathologically confirmed EC from 01/2016 to 06/2023. 166(46.8%) were classified as intermediate-to-high-risk ECs according to the European Society for Medical Oncology guidelines. Radiomics clustering analysis was performed on preoperative MRI to identify the radiomics phenotype of intermediate-to-high-risk ECs. The association between the radiomics phenotypes and the clinicopathologic information was explored, and the added value in predicting the recurrence was also evaluated using concordance index (C-index). RESULTS: Of the included 166 patients (average age 56.83 ± 9.25 years), 23 were recurrent patients. The corresponding tumors in various clusters were assigned to phenotypes 1 and 2. Larger tumor diameter (P < .01), cervical mucosa invasion [30(36.15%) vs 15(18.07%), P = .01], deep myometrial infiltration [51(61.45%) vs 31(37.35%), P = .00], and histologic subtype [17(20.48%) vs 5(6.02%), P = .01] were associated with subtype 1. The risk of recurrence (P = .01) was higher in phenotype 1, and the FIGO stage could further differentiate higher recurrence risk in phenotype 1 (P < .01). The C-index was 0.66 for the radiomics phenotype model, 0.69 for the FIGO stage model, and 0.72 for the combined model. CONCLUSIONS: MRI-based radiomics consensus clustering enabled the identification of associations between radiomics features and histopathologic features in intermediate-to-high-risk EC. The FIGO stage could further elevate the prediction ability of recurrence risk.

4.
Int J Biol Sci ; 20(11): 4513-4531, 2024.
Article in English | MEDLINE | ID: mdl-39247812

ABSTRACT

Large-scale phase III clinical trials of Olaparib have revealed benefits for ovarian cancer patients with BRCA gene mutations or homologous recombination deficiency (HRD). However, fewer than 50% of ovarian cancer patients have both BRCA mutations and HRD. Therefore, improving the effect of Olaparib in HR-proficient patients is of great clinical value. Here, a combination strategy comprising Olaparib and CDK12-IN-3 effectively inhibited the growth of HR-proficient ovarian cancer in cell line, patient-derived organoid (PDO), and mouse xenograft models. Furthermore, the combination strategy induced severe DNA double-strand break (DSB) formation, increased NHEJ activity in the G2 phase, and reduced HR activity in cancer cells. Mechanistically, the combination treatment impaired Ku80 poly(ADP-ribosyl)ation (PARylation) and phosphorylation, resulting in PARP1-Ku80 complex dissociation. After dissociation, Ku80 occupancy at DSBs and the resulting Ku80-primed NHEJ activity were increased. Owing to Ku80-mediated DNA end protection, MRE11 and Rad51 foci formation was inhibited after the combination treatment, suggesting that this treatment suppressed HR activity. Intriguingly, the combination strategy expedited cGAS nuclear relocalization, further suppressing HR and, conversely, increasing genomic instability. Moreover, the inhibitory effect on cell survival persisted after drug withdrawal. These findings provide a rationale for the clinical application of CDK12-IN-3 in combination with Olaparib.


Subject(s)
Genomic Instability , Ovarian Neoplasms , Phthalazines , Piperazines , Phthalazines/pharmacology , Phthalazines/therapeutic use , Piperazines/pharmacology , Piperazines/therapeutic use , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/genetics , Humans , Animals , Cell Line, Tumor , Mice , Genomic Instability/drug effects , Cell Death/drug effects , Cyclin-Dependent Kinases/metabolism , Ku Autoantigen/metabolism , DNA Breaks, Double-Stranded/drug effects
5.
JMIR Med Educ ; 10: e52784, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39140269

ABSTRACT

Background: With the increasing application of large language models like ChatGPT in various industries, its potential in the medical domain, especially in standardized examinations, has become a focal point of research. Objective: The aim of this study is to assess the clinical performance of ChatGPT, focusing on its accuracy and reliability in the Chinese National Medical Licensing Examination (CNMLE). Methods: The CNMLE 2022 question set, consisting of 500 single-answer multiple choices questions, were reclassified into 15 medical subspecialties. Each question was tested 8 to 12 times in Chinese on the OpenAI platform from April 24 to May 15, 2023. Three key factors were considered: the version of GPT-3.5 and 4.0, the prompt's designation of system roles tailored to medical subspecialties, and repetition for coherence. A passing accuracy threshold was established as 60%. The χ2 tests and κ values were employed to evaluate the model's accuracy and consistency. Results: GPT-4.0 achieved a passing accuracy of 72.7%, which was significantly higher than that of GPT-3.5 (54%; P<.001). The variability rate of repeated responses from GPT-4.0 was lower than that of GPT-3.5 (9% vs 19.5%; P<.001). However, both models showed relatively good response coherence, with κ values of 0.778 and 0.610, respectively. System roles numerically increased accuracy for both GPT-4.0 (0.3%-3.7%) and GPT-3.5 (1.3%-4.5%), and reduced variability by 1.7% and 1.8%, respectively (P>.05). In subgroup analysis, ChatGPT achieved comparable accuracy among different question types (P>.05). GPT-4.0 surpassed the accuracy threshold in 14 of 15 subspecialties, while GPT-3.5 did so in 7 of 15 on the first response. Conclusions: GPT-4.0 passed the CNMLE and outperformed GPT-3.5 in key areas such as accuracy, consistency, and medical subspecialty expertise. Adding a system role insignificantly enhanced the model's reliability and answer coherence. GPT-4.0 showed promising potential in medical education and clinical practice, meriting further study.


Subject(s)
Educational Measurement , Licensure, Medical , Humans , China , Educational Measurement/methods , Educational Measurement/standards , Reproducibility of Results , Clinical Competence/standards
6.
Eur J Radiol ; 178: 111622, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39018648

ABSTRACT

PURPOSE: To investigate the value of microstructural characteristics derived from time-dependent diffusion MRI in distinguishing high-grade serous ovarian cancer (HGSOC) from serous borderline ovarian tumor (SBOT) and the associations of immunohistochemical markers with microstructural features. METHODS: Totally 34 HGSOC and 12 SBOT cases who received preoperative pelvic MRI were retrospectively included in this study. Two radiologists delineated the tumors to obtain the regions of interest (ROIs). Time-dependent diffusion MRI signals were fitted by the IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) model, to extract microstructural parameters, including fraction of the intracellular component (fin), cell diameter (d), cellularity and extracellular diffusivity (Dex). Apparent diffusion coefficient (ADC) values were obtained from standard diffusion-weighted imaging (DWI). The parameters of HGSOCs and SBOTs were compared, and the diagnostic performance was evaluated. The associations of microstructural indexes with immunopathological parameters were assessed, including Ki-67, P53, Pax-8, ER and PR. RESULTS: In this study, fin, cellularity, Dex and ADC had good diagnostic performance levels in differentiating HGSOC from SBOT, with AUCs of 0.936, 0.909, 0.902 and 0.914, respectively. There were no significant differences in diagnostic performance among these parameters. Spearman analysis revealed in the HGSOC group, cellularity had a significant positive correlation with P53 expression (P = 0.028, r = 0.389) and Dex had a significant positive correlation with Pax-8 expression (P = 0.018, r = 0.415). ICC showed excellent agreement for all parameters. CONCLUSION: Time-dependent diffusion MRI had value in evaluating the microstructures of HGSOC and SBOT and could discriminate between these tumors.


Subject(s)
Diffusion Magnetic Resonance Imaging , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , Diffusion Magnetic Resonance Imaging/methods , Middle Aged , Diagnosis, Differential , Retrospective Studies , Adult , Aged , Cystadenocarcinoma, Serous/diagnostic imaging , Cystadenocarcinoma, Serous/pathology , Neoplasm Grading , Sensitivity and Specificity , Reproducibility of Results
7.
Cancer Manag Res ; 16: 559-573, 2024.
Article in English | MEDLINE | ID: mdl-38855329

ABSTRACT

Purpose: To investigate prognostic factors affecting cancer-specific survival (CSS) and to analyze the survival outcomes of patients with undifferentiated and dedifferentiated endometrial carcinoma (UDEC) who underwent various postoperative adjuvant therapies. Methods: The independent risk factors affecting CSS were studied using univariate and multivariate Cox regression analysis, and CSS in the presence of various postoperative treatments was evaluated using Kaplan-Meier method based on the cohort with pathologically confirmed UDEC from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, the study included 18 cases with UDEC in our center and explored their molecular characteristics and prognosis. Results: Between 2000 and 2019, a total of 443 patients were included from the SEER database. The median CSS duration was 14 months, with corresponding 3- and 5-year CSS rates of 45.9% and 44.0%, respectively. Factors such as pTNM stage, surgical resection of primary lesion, and chemoradiation independently influenced CSS. Postoperative chemotherapy alone improved CSS in patients with initial tumor spread beyond the uterus (pT3 and pT4), or lymph node (LN) invasion, or distant metastases. Additionally, postoperative radiotherapy enhanced CSS in patients who had undergone postoperative chemotherapy, those with primary tumors progressing to stage pT3, and those with LN involvement but without distant metastases. Of the 18 patients diagnosed at our center, with a median follow-up of 15.5 months, one experienced relapse and two succumbed to UDEC, who exhibited aberrant p53 expression in immunohistochemical staining. Conclusion: Postoperative chemotherapy and radiotherapy are beneficial for UDEC patients with tumors extending beyond the uterus or involving lymph nodes.

8.
Molecules ; 29(11)2024 May 22.
Article in English | MEDLINE | ID: mdl-38893320

ABSTRACT

Lipases, crucial catalysts in biochemical synthesis, find extensive applications across industries such as food, medicine, and cosmetics. The efficiency of lipase-catalyzed reactions is significantly influenced by the choice of solvents. Polar organic solvents often result in a decrease, or even loss, of lipase activity. Conversely, nonpolar organic solvents induce excessive rigidity in lipases, thereby affecting their activity. While the advent of new solvents like ionic liquids and deep eutectic solvents has somewhat improved the activity and stability of lipases, it fails to address the fundamental issue of lipases' poor solvent tolerance. Hence, the rational design of lipases for enhanced solvent tolerance can significantly boost their industrial performance. This review provides a comprehensive summary of the structural characteristics and properties of lipases in various solvent systems and emphasizes various strategies of protein engineering for non-aqueous media to improve lipases' solvent tolerance. This study provides a theoretical foundation for further enhancing the solvent tolerance and industrial properties of lipases.


Subject(s)
Lipase , Solvents , Lipase/chemistry , Lipase/metabolism , Solvents/chemistry , Protein Engineering , Enzyme Stability , Biocatalysis , Ionic Liquids/chemistry
9.
Clin Transl Oncol ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38904923

ABSTRACT

OBJECTIVE: The survival benefit of first-line treatment with bevacizumab in advanced ovarian cancer patients are multifaceted. In our study, we aimed to identify potential markers of bevacizumab efficacy to help predict which patients would experience survival benefits. METHODS: This was a retrospective analysis of 114 patients examined from January 1, 2015, to March 1, 2023, and data on clinical, biological, and imaging variables, such as ascites, serum LDH, and CA125, were extracted from electronic medical records. We performed a correlation analysis and principal component analysis to investigate correlations among variables and reduce their dimensionality. Then, univariate and multivariate Cox proportional hazards regression analyses were used to identify the predictors of progression-free survival. RESULTS: Favorable KELIM score (≥ 1, HR 0.376, 95% CI [0.202-0.700], p = 0.002), which indicated better chemosensitivity, and lower LDH levels (≤ 210 U/L, HR 38.73, 95% CI [6.108-245.6], p < 0.001) were found to be independent predictors of a treatment benefit with bevacizumab in patients with advanced ovarian cancer. Regardless of LDH level, patients with favorable KELIM scores had a higher progression-free survival (PFS) benefit (p = 0.18). Among patients with unfavorable KELIM scores, those with higher LDH levels had the lowest PFS benefit (median: 11.5 months, p = 0.0059). CONCLUSION: Patients with poor chemosensitivity and low LDH levels are more likely to benefit from first-line bevacizumab treatment. The combination of the two markers can be a helpful predictor of patients who are most likely to benefit from treatment and a guide for treatment decisions-making. Retrospectively registered: 2020-MD-371, 2020.10.12.

10.
Cancer Lett ; 597: 217064, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38880223

ABSTRACT

Platinum-based chemotherapy causes genetic damage and induces apoptosis in ovarian cancer cells. Enhancing the ability to resist platinum drug-induced DNA damage and apoptotic stress is critical for tumor cells to acquire drug resistance. Here, we found that Y-box binding protein 1 (YBX1) was highly expressed in cisplatin-resistant patient-derived organoids (PDOs) and was a crucial gene for alleviating platinum-induced stress and maintaining drug resistance characteristics in ovarian cancer cells. Mechanistically, YBX1 recognized m5C modifications in CHD3 mRNA and maintained mRNA stability by recruiting PABPC1 protein. This regulatory process enhanced chromatin accessibility and improved the efficiency of homologous recombination (HR) repair, facilitating tumor cells to withstand platinum-induced apoptotic stress. In addition, SU056, an inhibitor of YBX1, exhibited the potential to reverse platinum resistance in subcutaneous and PDO orthotopic xenograft models. In conclusion, YBX1 is critical for ovarian cancer cells to alleviate the platinum-induced stress and may be a potential target for reversing drug-resistant therapies.


Subject(s)
Cisplatin , Drug Resistance, Neoplasm , Ovarian Neoplasms , Y-Box-Binding Protein 1 , Humans , Female , Y-Box-Binding Protein 1/metabolism , Y-Box-Binding Protein 1/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Animals , Cisplatin/pharmacology , Cell Line, Tumor , Mice , Xenograft Model Antitumor Assays , Homologous Recombination/drug effects , Apoptosis/drug effects , DNA Helicases/genetics , DNA Helicases/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Antineoplastic Agents/pharmacology , DNA Damage/drug effects
12.
Biomed Pharmacother ; 175: 116733, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38754267

ABSTRACT

The introduction of PARP inhibitors (PARPis) and immune checkpoint inhibitors (ICIs) has marked a significant shift in the treatment landscape for solid tumors. Emerging preclinical evidence and initial clinical trials have indicated that the synergistic application of PARPis and ICIs may enhance treatment efficacy and potentially improve long-term patient outcomes. Nonetheless, how to identify specific tumor types and molecular subgroups most likely to benefit from this combination remains an area of ongoing research. This review thoroughly examines current studies on the co-administration of PARPis and ICIs across various solid tumors. It explores the underlying mechanisms of action, evaluates clinical efficacy, identifies potential responder populations, and delineates common adverse events alongside strategic management approaches. The aim is to offer a detailed understanding of this combination therapy, potentially guiding future therapeutic strategies for solid tumors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Immune Checkpoint Inhibitors , Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/pharmacology , Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Animals
13.
Ann Surg Oncol ; 31(8): 5111-5114, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38730117

ABSTRACT

BACKGROUND: Due to previous surgical history and subsequent adhesions between pelvic organs, surgery for cervical stump cancer (CSC) is technically more challenging than surgery for cervical cancer with an intact uterus.1 We aimed to illustrate the related anatomy, surgical steps and techniques of complete laparoscopic type C2 radical surgery (CLRS) for early-stage CSC. METHODS: CLRS for six patients with CSC was performed from January 2021 to January 2022. We demonstrated the detailed skills of parametrial management during CLRS for CSC in case 5 by means of a video. A 58-year-old woman diagnosed with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1 CSC received CLRS through five operative ports (Fig. 1). RESULTS: The magnetic resonance imaging (MRI) scans and gross appearance of the specimen are shown in Fig. 2. The median age and body mass index (BMI) of the six patients were 53 years and 23.8, respectively. The median blood loss was 275 mL; the median time of operation was 218 min; the median length of hospitalization was 15 days; and the median time to recover urinary function was 12 days. One patient underwent postoperative radiation for pathologically proven adenocarcinoma with deep stromal invasion,2 while the other five did not. After a median follow-up of 24 months, no patients experienced complications, recurrence, or death (Table 1). CONCLUSIONS: This study details the skills of CLRS for CSC, especially space development and the 'no-look, no-touch' tumor-free principle. It is helpful for clinicians to perform safe and standardized surgery on patients with early-stage CSC. Fig. 1 Trocar placement of complete laparoscopic type C2 radical surgery for early-stage CSC. CSC cervical stump cancer, S superior, I inferior, R right, L left, U umbilicus Fig. 2 MRI scans and gross appearance of the specimen for case 5 with CSC at FIGO 2018 stage IIA1. The tumor lesion on the cervical stump is indicated by yellow arrows. a Axial T2-weighted image; b DKI image; c ADC map; d sagittal T2-weighted image; e sagittal T1-weighted image; f gross appearance of the surgical specimen. MRI magnetic resonance imaging, CSC cervical stump cancer, FIGO International Federation of Gynecology and Obstetrics, DKI diffusional kurtosis imaging, ADC apparent diffusion coefficient Table 1 Clinicopathological characteristics, operative details, and outcomes of patients with cervical stump cancer Patient no. Age at diagnosis (years) BMI Reasons for subtotal hysterectomy FIGO 2018 stage Histology Operation Operation time (mins) Blood loss (mL) Urinary catheter (days) Hospital stay (days) Complications Depth of invasion LVSI LNs dissected TNM stage Tumor size (mm) Postoperative radiotherapy Follow-up (months) Recurrence Death 1 50 25.9 Uterine myoma IIA1 ASC CLRS+PLND 221 360 10 12 No Middle one-third N 13 T2a1N0M0 16 No 30 No No 2 55 17.3 Uterine myoma IB1 AC CLRS+PLND 191 270 20 12 No Deep one-third N 24 T1b1N0M0 10 Yes 20 No No 3 50 24.8 Uterine myoma IB1 SC CLRS+PLND 295 310 13 15 No Superficial one-third N 21 T1b1N0M0 15 No 25 No No 4 63 30.1 Uterine myoma IB1 SC CLRS+PLND 213 180 6 16 No Superficial one-third N 25 T1b1N0M0 15 No 19 No No 5 58 20.2 Postpartum hemorrhage IIA1 SC CLRS+PLND 220 100 11 14 No Middle one-third N 21 T2a1N0M0 15 No 24 No No 6 46 22.7 Uterine myoma IB1 SC CLRS+PLND 215 120 14 17 No Superficial one-third N 26 T1b1N0M0 12 No 23 No No BMI body mass index, FIGO International Federation of Gynecology and Obstetrics, ASC cervical adenosquamous carcinoma, AC cervical adenocarcinoma, SC cervical squamous carcinoma, CLRS+PLND complete laparoscopic radical surgery and pelvic node dissections, LVSI lymphovascular space invasion, N negative, LNs lymph nodes, TNM tumor node metastasis.


Subject(s)
Laparoscopy , Uterine Cervical Neoplasms , Humans , Female , Laparoscopy/methods , Middle Aged , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/pathology , Prognosis , Follow-Up Studies , Hysterectomy/methods , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Neoplasm, Residual/surgery , Neoplasm, Residual/pathology
14.
Cancer Rep (Hoboken) ; 7(3): e2046, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38507268

ABSTRACT

BACKGROUND: Ovarian granulosa cell tumors (OGCTs) feature low incidence, indolent growth and late recurrence. Treatment for recurrent OGCTs is challenging. METHODS: The present study was designed to explore the prognostic factors and establish a nomogram to predict cancer-specific survival (CSS) for OGCTs patients. Enrolled in the study were 1459 eligible patients in the Surveillance, Epidemiology, and End Results (SEER) database, who were randomized to the training (n = 1021) or testing set (n = 438) at a ratio of 7:3. Univariate and multivariate Cox regression analyses were employed to screen the prognostic factors. The predictors were determined by using the Least absolute shrinkage and selection operator (LASSO) regression analysis. The model was constructed via the Cox proportional hazards risk regression analysis. The performance and clinical value of the nomograms was assessed with C-index, calibration plots, and decision curve analysis. RESULTS: Age, pTNM stage, tumor size, surgery of the primary tumor, surgery of regional lymph nodes (LNs), residual disease after surgery, and chemotherapy were considered as significant predictive factors for CSS in OGCTs patients. After screening, the prognostic factors except surgery of regional LNs and chemotherapy were employed to build the nomogram. With desirable discrimination and calibration, the nomogram was more powerful in predicting CSS than the American Joint Committee on Cancer staging system in clinical use. CONCLUSION: This novel prognostic nomogram, which comprises a stationary nomogram and a web-based calculator, offers convenience for clinicians in personalized decision-making including optimal treatment plans and prognosis assessments for OGCTs patients.


Subject(s)
Granulosa Cell Tumor , Nomograms , Humans , Female , Prognosis , Granulosa Cell Tumor/diagnosis , Granulosa Cell Tumor/therapy , Databases, Factual
15.
Cell Death Differ ; 31(4): 497-510, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38374229

ABSTRACT

Poly ADP-ribose polymerase inhibitors (PARPis) exhibit promising efficacy in patients with BRCA mutations or homologous repair deficiency (HRD) in ovarian cancer (OC). However, less than 40% of patients have HRD, it is vital to expand the indications for PARPis in BRCA-proficient patients. Ferroptosis suppressor protein 1 (FSP1) is a key protein in a newly identified ferroptosis-protective mechanism that occurs in parallel with the GPX4-mediated pathway and is associated with chemoresistance in several cancers. Herein, FSP1 is reported to be negatively correlated with the prognosis in OC patients. Combination therapy comprising olaparib and iFSP1 (a FSP1 inhibitor) strongly inhibited tumour proliferation in BRCA-proficient OC cell lines, patient-derived organoids (PDOs) and xenograft mouse models. Surprisingly, the synergistic killing effect could not be reversed by ferroptosis inhibitors, indicating that mechanisms other than ferroptosis were responsible for the synergistic lethality. In addition, cotreatment was shown to induce increased γH2A.X foci and to impair nonhomologous end joining (NHEJ) activity to a greater extent than did any single drug. Mass spectrometry and immunoprecipitation analyses revealed that FSP1 interacted with Ku70, a classical component recruited to and occupying the end of double-strand breaks (DSBs) in the NHEJ process. FSP1 inhibition decreased Ku70 PARylation, impaired subsequent DNA-PKcs recruitment to the Ku complex at DSB sites and was rescued by restoring PARylation. These findings unprecedentedly reveal a novel role of FSP1 in DNA damage repair and provide new insights into how to sensitize OC patients to PARPi treatment.


Subject(s)
Ferroptosis , Ovarian Neoplasms , Phthalazines , Piperazines , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Ovarian Neoplasms/genetics , Female , Phthalazines/pharmacology , Phthalazines/therapeutic use , Piperazines/pharmacology , Piperazines/therapeutic use , Animals , Mice , Ferroptosis/drug effects , Cell Line, Tumor , BRCA1 Protein/metabolism , BRCA1 Protein/genetics , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Cell Proliferation/drug effects , S100 Calcium-Binding Protein A4/metabolism , S100 Calcium-Binding Protein A4/genetics
16.
Cancer Cell Int ; 24(1): 42, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38273320

ABSTRACT

BACKGROUND: Circular RNAs (circRNAs) are involved in the regulation of progression and drug resistance in ovarian cancer (OC). In the present study, we aimed to explore the role of circRAD23B, a newly identified circRNA, in the regulation of carboplatin-resistant OC. METHODS: CircRAD23B expression levels were measured using qRT-PCR. The biological roles of circRAD23B were analysed using CCK-8, colony formation, EDU, flow cytometry, and cell viability assays. RNA pull-down and luciferase assays were used to investigate the interactions of circRAD23B with mRNAs and miRNAs. RESULTS: CircRAD23B was significantly increased in carboplatin-resistant OC tissues. CircRAD23B promoted proliferation and reduced sensitivity to carboplatin in cell lines and patient-derived organoids (PDOs), consistent with in vivo findings. Mechanistically, circRAD23B acted as a molecular sponge, abrogating its inhibitory effect on Y-box binding protein 1 (YBX1) by adsorbing miR-1287-5p. Rescue experiments confirmed that the pro-proliferation and carboplatin resistance mediated by circRAD23B was partially reversed by the upregulation of miR-1287-5p. CONCLUSIONS: Our results demonstrated, for the first time, the role of the circRAD23B/miR-1287-5p/YBX1 axis in OC progression and carboplatin resistance in cell lines, PDOs, and animal models, providing a basis for the development of targeted therapies for patients with OC.

17.
BMC Surg ; 24(1): 9, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38172752

ABSTRACT

BACKGROUND: To compare the impact of surgical approach on progression free survival (PFS) stratified by histologic type in women diagnosed with stage IA endometrial cancer. METHODS: Myometrial invasion is classified into no myometrial invasion, <50% and ≥50%, with only no myometrial invasion and <50% are included in stage IA patients. A retrospective study is designed by collecting data from women diagnosed as stage IA endometrial cancer from January 2010 to December 2019 in a tertiary hospital. A propensity score is conducted for 1:1 matching in the low-risk histologic patients. Progression free survival and disease-specific survival data are evaluated by the Kaplan-Meier method and compared by the log-rank test in both the whole population and the matched-pair groups. A sub-group analysis is performed to figure out risk factors associated with the effect of surgical approach on PFS and disease-specific survival (DSS). RESULTS: 534 (84.49%) low-risk histologic endometrial cancer women, with 389 (72.85%) operated by minimally invasive surgery and 145 (27.15%) by open approach, and 98 (15.51%) high-risk histology, with 71 (72.45%) by laparoscopy and 27 (27.55%) by open surgery, are included. Compared to open surgery, laparoscopy results in lower progression free survival in low-risk patients before and after matching (p = 0.039 and p = 0.033, respectively), but shows no difference in high-risk patients (p = 0.519). Myometrial invasion is associated with lower progression free survival in laparoscopy in low-risk histology (p = 0.027). CONCLUSION: Surgical approaches influence progression free survival in stage IA low-risk histologic diseases, especially in those with myometrial invasion, but not in high-risk histologic endometrial cancer.


Subject(s)
Endometrial Neoplasms , Humans , Female , Treatment Outcome , Retrospective Studies , Matched-Pair Analysis , Neoplasm Staging , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathology
18.
J Cancer Res Clin Oncol ; 150(1): 19, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38243112

ABSTRACT

PURPOSE: The preoperative diagnosis of endometriosis associated ovarian cancer (EAOC) remains challenging for lack of effective diagnostic biomarker. We aimed to study clinical characteristics and develop a nomogram for diagnosing EAOC before surgery. METHODS: A total of 87 patients with EAOC and 348 patients with ovarian endometrioma (OEM) were enrolled in our study. Least absolute shrinkage and selection operator (LASSO) regression and Logistic regression were utilized to select variables and construct the prediction model. The performance of the model was assessed using receiver operating characteristic (ROC) analyses and calibration plots, while decision curve analyses (DCAs) were conducted to assess clinical value. Bootstrap resampling was used to evaluated the stability of the model in the derivation set. RESULTS: The EAOC patients were older compared to the OEM patients (46.41 ± 9.62 vs. 36.49 ± 8.09 year, P < 0.001) and proportion of postmenopausal women was higher in EAOC group than in the OEM group (34.5 vs. 1.5%, P < 0.001). Our prediction model, which included age at diagnosis, tumor size, cancer antigen (CA) 19-9 and risk of ovarian malignancy algorithm (ROMA), demonstrated an area under the curve (AUC) of 0.858 (95% confidence interval (CI): 0.795-0.920) in the derivation set (N = 304) and an AUC of 0.870 (95% CI: 0.779-0.961) in the validation set (N = 131). The model fitted both the derivation (Hosmer-Lemeshow test (HL) chi-square = 12.600, P = 0.247) and the validation (HL chi-square = 8.210, P = 0.608) sets well. CONCLUSION: Compared to patients with OEM, those with EAOC exhibited distinct clinical characteristics. Our four-variable prediction model demonstrated excellent performance in both the derivation and validation sets, suggesting its potential to assist with preoperative diagnosis of EAOC.


Subject(s)
Endometriosis , Ovarian Neoplasms , Humans , Female , Endometriosis/complications , Endometriosis/diagnosis , Endometriosis/surgery , Nomograms , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Ovarian Neoplasms/pathology , ROC Curve
19.
Eur J Obstet Gynecol Reprod Biol ; 294: 97-104, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38219610

ABSTRACT

OBJECTIVE: This study was designed to investigate the relationship between the Gustave-Roussy immune score (GRIm-score) and platinum resistance in patients with advanced high-grade serous ovarian cancer (HGSOC). METHODS: We conducted a retrospective study of patients diagnosed with advanced HGSOC between January 2017 and December 2020. A nomogram was developed to predict the risk of platinum resistance. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to validate the nomogram. Bootstrap analysis was utilized for internal validation. Additionally, we analyzed the risk factors for platinum resistance in patients who received neoadjuvant chemotherapy (NACT). RESULTS: A total of 232 patients with advanced HGSOC were included, 52 (22.4 %) of whom experienced relapse with platinum resistance. Multivariate logistic regression analysis revealed that high GRIm-score (OR = 4.174, P < 0.001), NACT (OR = 2.706, P = 0.017), PLT > 260 (OR = 2.233, P = 0.037) and non-R0 (OR = 2.526, P = 0.012) were independent risk factors for platinum resistance. The area under the curve (AUC) of the model was 0.802 (95 % CI 0.736-0.868), and the internally validated AUC of 1000 bootstrap samples was 0.798 (95 % CI 0.725-0.862). In NACT-treated patients, univariate and multivariate logistic regression analyses revealed that a low KELIM score (OR = 10.405, P = 0.001) and PLT > 260 (OR = 4.611, P = 0.014) were independent risk factors for platinum resistance. CONCLUSION: The GRIm-score and PLT count are important prognostic factors in patients with HGSOC. For precision treatment, the status of partially platinum-sensitive patients should also be considered.


Subject(s)
Ovarian Neoplasms , Platinum , Humans , Female , Platinum/therapeutic use , Ovarian Neoplasms/drug therapy , Retrospective Studies , Neoplasm Recurrence, Local , Nomograms
20.
Arch Gynecol Obstet ; 309(4): 1491-1498, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37698603

ABSTRACT

OBJECTIVE: To explore the association between visceral obesity and short-term postoperative complications in patients with advanced ovarian cancer undergoing cytoreductive surgery. METHODS: The medical records of patients with advanced epithelial ovarian cancer were reviewed. The visceral fat area, subcutaneous fat area and total fat area at the L3/4 level were measured on a preoperative single-slice CT scan. The receiver operating characteristic (ROC) curve was used to calculate the optimal cutoff value for the visceral fat area. The relationship between the visceral fat area and the characteristics of ovarian cancer patients were analyzed. Univariable and multivariable logistic regression analyses were performed to investigate relationship between perioperative characteristics and short-term complications. RESULTS: According to the ROC curve, the best cutoff value of the VFA was 93 cm2. Of the 130 patients, 53.8% (70/130) had visceral obesity. Patients with visceral obesity were older than those with nonvisceral obesity (58.4 years old vs. 52.1 years old, p < 0.001). The proportion of patients with hypertension was higher (35.7 vs. 13.3%, p = 0.003). The total fat area and subcutaneous fat area were larger in patients with visceral obesity (294.3 ± 75.5 vs. 176.2 ± 68.7, p < 0.001; 158.9 ± 54.7 vs. 121.7 ± 52.6, p < 0.001). Compared with patients in the nonvisceral obese group, patients in the visceral obese group were more likely to have postoperative fever (21/70 30.0% vs. 8/60 1.25%, p = 0.023), leading to a longer length of hospital stay (21 days vs. 17 days, p = 0.009). The time from surgery to adjuvant chemotherapy for patients with visceral obesity was shorter (24 days vs. 19 days, p = 0.037). Multivariate analysis showed that visceral obesity (OR = 6.451, p < 0.001) and operation time (OR = 1.006, p < 0.001) were independent predictors of postoperative complications. CONCLUSION: Visceral obesity is an important risk factor for short-term postoperative complications in patients with advanced ovarian cancer undergoing cytoreductive surgery.


Subject(s)
Obesity, Abdominal , Ovarian Neoplasms , Humans , Female , Middle Aged , Obesity, Abdominal/complications , Obesity/complications , Risk Factors , Tomography, X-Ray Computed , Ovarian Neoplasms/complications , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/surgery , Postoperative Complications/diagnostic imaging , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Carcinoma, Ovarian Epithelial/diagnostic imaging , Carcinoma, Ovarian Epithelial/complications , Retrospective Studies , Body Mass Index
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