Qian Zhang

The vasculogenic mimicry, CD146 + and CD105 + microvessel density in the prognosis of endometrioid endometrial adenocarcinoma: a single-centre immunohistochemical study

The microvessel compartment is crucial in the tumour microenvironment of endometrioid adenocarcinoma (EA). This study investigated the role of vasculogenic mimicry (VM), CD146, and CD105 microvessel density in the clinical prognosis of EA. A total of 188 EA cases were analyzed, with VM channels and microvessels detected using PAS/CD31, CD146, and CD105 staining. Mann-Whitney and Fisher exact tests were used to compare the study groups according to the evaluated criteria. ROC analysis included determination of the confidence interval (CI) and area under the ROC curve. The Mantel-Cox test was used to analyze progression-free survival. Multivariate Cox proportional hazard analysis was performed using stepwise regression. Results showed that VM channels and CD146 and CD105 microvessels were significantly higher (

Long-Term Follow-up of Levonorgestrel Intrauterine Device for Atypical Hyperplasia and Early Endometrial Cancer Reveals Relapse Characterized by Immune Exhaustion

Abstract Purpose: Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited. Materials and Methods: Follow-up data from patients in our prospective phase II trial of levonorgestrel intrauterine device (LIUD) for AH/G1EEC were collected from medical records. Spatial transcriptomics (Nanostring GeoMX digital spatial profiling) with in silico cell type deconvolution and pathway analyses were employed on longitudinal biopsy samples from five patients across pre-treatment, on-treatment, and relapse. Results: Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen (39%) experienced relapse. Clinical factors associated with shorter response duration included younger age, initial diagnosis of G1EEC, lack of response at 6 months, premenopausal status, and Hispanic ethnicity (P < 0.05), but only 6-month response status remained a significant predictor in a multivariate model (P = 0.023). LIUD increased abundance of NK cells (ΔMCP-counter score = 46.13, FDR = 0.004) and cytotoxic lymphocytes (ΔMCP-counter score = 277.67, FDR = 0.004), as well as lymphocyte cytotoxicity markers PRF1 (log2FC = 1.62, FDR = 0.025) and GZMA (log2FC = 2.47, FDR = 0.008). NK cells were reduced at relapse (ΔMCP-counter score = −55.96, FDR = 0.02). Immune-related pathways (IFNα response and TGFβ signaling) were enriched at relapse (FDR < 0.05). IDO1 expression, reflecting immune exhaustion, was upregulated at relapse (FDR < 0.05). Conclusions: Upfront resistance and relapse after initial response to LIUD for AH/G1EEC impacts nearly half of patients, remaining a major hurdle for nonsurgical treatment of AH/G1EEC. Molecular studies evaluating longitudinal biopsies from a small cohort implicate immune mechanisms at relapse, including reversal of progestin-related immunomodulation and increased immune exhaustion. See related commentary by Johannet and Friedman, p. 5001

Everolimus, Letrozole, and Metformin in Women with Advanced or Recurrent Endometrioid Endometrial Cancer: A Multi-Center, Single Arm, Phase II Study

Abstract Purpose: Treatment for patients with recurrent endometrioid endometrial cancer (EEC) are limited as paclitaxel is the only second-line chemotherapy with a response rate >13%. Targeting PIK3/mTOR in combination with hormonal therapy has shown promise. The addition of metformin may enhance this response. We conducted a phase II study evaluating everolimus, letrozole, and metformin in advanced/recurrent EEC. Patients and Methods: A Simon two-stage design was employed. Women with ≤2 prior chemotherapy regimens for recurrence were eligible. Pretreatment biopsy was required, followed by everolimus 10 mg orally, letrozole 2.5 mg orally, and metformin 500 mg orally twice a day on a 4-week cycle. The primary endpoint was clinical benefit (CB), defined as complete response (CR), partial response (PR), or stable disease (SD) confirmed at 16 weeks. Patients were treated until progression or toxicity. Results: Sixty-two patients were enrolled. Median age was 62 years (40–77) with 401 cycles completed, median of 6 cycles (1–31). Fifty-four patients were evaluable for response with a CB rate of 50% (27/54). Best overall response (OR) was PR 28% (15/54) and SD 22% (12/54). Thirteen patients received >12 cycles. Median follow-up was 17.9 months (2–47). Median progression-free survival was 5.7 [95% confidence interval (CI), 3.0–8.1] and OS was 19.6 months (95% CI, 14.2–26.3). Positive progesterone receptor expression was associated with CB (89.5% vs. 27.3%, P = 0.001). Conclusions: Everolimus, letrozole, and metformin resulted in 50% CB and 28% OR in women with recurrent EEC. Progesterone receptor–positive tumors may have better response; validation studies are needed. See related commentary by Madariaga et al., p. 523

RETRACTED: Diagnostic value for methylation in cervical cancer based on a small‐molecule fluorescent probe targeting DNMT1

Abstract Background Value analysis of a small‐molecule fluorescent probe for methylation detection in different cervical lesions. Materials and Methods (1) The grayscale values of distinct lesion tissues were remarkably distinct among the four groups ( p  < 0.05). The comparison of the grayscale value between the two groups showed that the CA group noticeably exceeded the LSIL and cervicitis groups, and the HSIL group was apparently higher than the LSIL and cervicitis groups ( p  < 0.05); (2) The mean grayscale values of the enrolled subjects were calculated with 55.21 as the midline, with >55.21 as positive and ≤55.21 as negative. Results The results showed that the positive rate of the cervicitis group was 0.00%, the LSIL group 67.74%, the HSIL group 83.33%, and the CA group 100.00%. The results among the four groups were notably distinct ( p <  0.05); (3) The comparison among DAPI, probe, bright, and merged images of cervicitis, LSIL, HSIL, and CA indicated that different cervical lesions were with quite various stains. Conclusion The grayscale value, positive rate, and stained picture of distinct cervical lesions were remarkably different. The small‐molecule fluorescent probe has a good value in differentiating cervical lesions and can be considered for popularization and application.

The transcription factor ZEB1 mediates the progression of epithelial ovarian cancer by promoting the transcription of CircANKRD17

AbstractZinc finger E‐box‐binding homeobox 1 (ZEB1) is a key transcription factor that regulates the process of epithelial‐mesenchymal transition (EMT) in various tumors. However, its role in epithelial ovarian cancer (EOC) is far from understood. The present study aimed to explore the role and potential mechanism of action of ZEB1 in EOC. A quantitative reverse transcription‐polymerase chain reaction was used to detect ZEB1 expression levels. The Cell Counting Kit‐8 assay, transwell assays, and flow cytometry were used to verify the effects of ZEB1 on the proliferation, invasion, migration, apoptosis, and EMT of EOC, respectively. RNA sequencing identified the effect of knocking down ZEB1 on circular RNAs in EOC cells. Dual‐luciferase activity assay and chromatin immunoprecipitation experiments were used to verify the regulatory effect of ZEB1 on the circular RNA ANKRD17 (CircANKRD17; ID: hsa_circ_0007883) at the transcriptional level. Higher ZEB1 expression was found in EOC tissues and cells and was closely related to tumor metastasis, advanced stages, and lower survival rates. Furthermore, silencing ZEB1 inhibited the proliferation, invasion, migration, and EMT of EOC cells but enhanced cell apoptosis. Mechanistically, knockdown of ZEB1 resulted in the greatest downregulation of CircANKRD17 in EOC cells, and ZEB1 significantly promoted the expression of CircANKRD17 and had no significant effect on ANKRD17 messenger RNA expression. Further experiments verified that ZEB1 mediates the regulation of EOC processes by CircANKRD17. Highly expressed ZEB1 promoted proliferation, invasion, migration, and EMT while it inhibited cell apoptosis in EOC by promoting the transcription of CircANKRD17, providing a potential target for the treatment of EOC.

Preventive effect of memory foam position pads on intraoperative pressure-induced skin injuries in gynecological malignancy patients undergoing lithotomy positioning

This study explores the effect of memory sponge body position pad on pressure injury of compressed skin in patients undergoing lithotomy. From October 2021 to March 2022, 94 adult patients with gynecological malignancies who underwent elective general anesthesia surgery in our hospital and were in the lithotomy position during the operation were selected as the research objects. According to the different kinds of nursing, they were divided into 47 cases in the control group and 47 cases in the experimental group. The control group used silicone gel pads, and the experimental group used memory sponge pads. The incidence of pressure injury (PI), postoperative comfort contact area and average pressure of pressure part, and the surface microenvironment of the pressure part were compared between the 2 groups. Compared with the control group (17.02%), the incidence of PI in the observation group (2.13%) was significantly lower (P < .05); Compared with the control group (12.77%, 17.02%, 21.28%), the incidence of limb numbness (0.00%), waist muscle pain (4.26%) and neck and shoulder pain (6.38%) in the observation group were significantly lower (P < .05); Compared with the control group, the contact area of the compressed part in the observation group increased significantly and the average pressure decreased significantly after anesthesia, after positioning, during and after operation (P < .05); Compared with the pressure for 1 hour, the humidity and temperature of the feet, buttocks, and shoulders of the 2 groups were significantly higher after 2 hours of pressure, while the humidity and temperature of the feet, buttocks, and shoulders were significantly lower in the observation group compared to the control group (P < .05). The memory sponge position pad can prevent the occurrence of PI on the compressed skin of patients undergoing lithotomy and can also improve the postoperative comfort of patients and the surface microenvironment of the compressed part, which has high clinical reference value.

Development of Covalent Small-Molecule Fluorescent Probes for DNA Methyltransferase 1 Detection in Cancer Cells and Cervical Exfoliated Cells

DNA methyltransferase 1 (DNMT1) overexpression is associated with aberrant methylation and tumorigenesis, making its detection vital for tumor diagnosis. In this study, RG108 derivatives bearing cysteine-targeted covalent moieties were constructed as warheads for the DNMT1 detectors. Following affinity assessment by surface plasmon resonance, warheads containing a 2-fluoroacrylamido moiety were selected for preparing fluorescein-labeled probes