Ming Wu

The clinicopathological characteristics and survival outcomes of endometrial carcinoma coexisting with or arising in adenomyosis: A pilot study

AbstractLittle is known about the epidemiological and clinicopathological characteristics of endometrial endometrioid carcinoma (EEC) coexisting with or arising in adenomyosis (EEC-A or EEC-AIA) due to their rarity. This study compared EEC-A and EEC-AIA with endometrial carcinoma without adenomyosis. Cases of endometrial cancer treated at the study center from June 1, 2010, to June 1, 2017, were reviewed. The epidemiological, clinicopathological characteristics and survival outcomes were compared among three groups of endometrioid subtypes: group A, stage IA endometrial carcinoma patients without coexisting adenomyosis; group B, patients with EEC-A; and group C, patients with EEC-AIA. Among the 2080 patients reviewed, groups A, B, and C included 1043, 230 and 28 patients, respectively. Patients in group A and group B had similar clinicopathological and survival outcomes. Patients in group C were significantly younger and had less gravidity and parity than patients in groups A and B. More tumors from group C were grade 1, and they had a smaller maximum diameter and less mismatch repair deficiency than those from groups A and B. After a median follow-up of 57.0 months, the 5-year disease-free survival (DFS) rates of groups A, B and C were 96%, 91% and 100% (p = 0.045), respectively; the 5-year overall survival (OS) rates were 98%, 93% and 100%, respectively (p = 0.001), in the Kaplan-Meier analysis. However, these difference disappeared in a subgroup of stage IA patients in univariate and multivariate analysis. Cox regression analysis in stage IA patients also revealed no significant differences in survival outcome across the three groups. In conclusion, EEC-AIA exhibited specific clinicopathological characteristics that were probably associated with favorable survival outcomes. The characteristics and survival outcomes of EEC-A were similar to those of EEC without adenomyosis in stage IA patients.

Neuroendocrine carcinoma of the cervix: the value of postoperative radiation in early-stage disease

The current treatment for early-stage neuroendocrine carcinoma of the cervix (NECC) mainly relies on operation and chemotherapy. We want to evaluate values of postoperative radiation in early-stage NECC. Retrospective cohort study. Early-stage NECC patients from 2006 to 2022 in our hospital were included and divided into Postoperative non-radiation group (Group A) and Postoperative radiation group (Group B). We use Kaplan-Meier method to analyze the progression-free survival (PFS), overall survival (OS), recurrence and OS rate. Sixty-six cases were included, 32 (48.5%) in Group A and 34 (51.5%) in Group B. After 35 (range 12-116) months follow-up, 26 (39.4%) had recurrence. Compared with Group A, Group B had lower pelvic recurrence rate (12.5% vs 2.9%, Retrospective study and relative small sample size. Postoperative radiation seems to prolong PFS and OS in patients with cervical stromal invasion ≥1/2. LVSI was a high-risk factor for tumour recurrence, but radiation after surgery in patients with LVSI seems have no survival benefits.

Circulating CD4+ Treg, CD8+ Treg, and CD3+ γδ T Cell Subpopulations in Ovarian Cancer

Background and Objectives: Regulatory T cells (Tregs) are usually enriched in ovarian cancer (OC), and their immunosuppressive function plays a key role in tumorigenesis and progression. We mainly explored the phenotypical characterization of Treg-related markers on αβ and γδ T cell subsets in patients with OC. Materials and Methods: Thirty-six untreated patients with OC at the Women’s Hospital of Nanjing Medical University from September 2019 to August 2021 were enrolled. Phenotypical characterization of Tregs-related markers were detected by flow cytometry (FCM). Enzyme-linked immunosorbent assay was used to detect the levels of carbohydrate antigen (CA125) and transforming growth factor β (TGF-β). The level of human epididymis protein 4 (HE4) was detected by electrochemiluminescence immunoassay. Results: Circulating CD4+ Tregs, CD8+ Tregs, and CD3+γδ T cell subpopulations from OC patients have elevated Foxp3, CD25, CD122, Vδ1, and reduced CD28 expression compared to benign ovarian tumor (BOT) patients and healthy controls (HC). The upregulation of Foxp3 and Vδ1 and the downregulation of CD28 were highly specific for maintaining the immunosuppression function of CD4+ Tregs, CD3+γδ T cells, and CD8+ Tregs in OC patients. These Treg subpopulations were able to discriminate OC from BOT and HC. The levels of CA125, HE4, and TGF-β were increased in OC patients. A significant positive correlation between Treg subpopulations and CA125, HE4, and TGF-β was revealed. Conclusions: Proportions of CD4+ Tregs, CD8+ Tregs, and CD3+γδ T cell subsets were significantly increased in OC patients and were positively correlated with FIGO stage/metastasis status, CA125, HE4, and TGF-β. These indicators have the potential to be used as immunosurveillance biomarkers for OC.

Multifunctional theranostic nanosystems enabling photothermal-chemo combination therapy of triple-stimuli-responsive drug release with magnetic resonance imaging

As a multifunctional theranostic nanoplatform, FPCH-DOX NPs enable triple-stimuli responsive drug release for MR/thermal imaging-guided photothermal-chemo combination therapy.

Multifunctional theranostic agents based on prussian blue nanoparticles for tumor targeted and MRI—guided photodynamic/photothermal combined treatment

Abstract The independence of photodynamic or photothermal modality create difficulties in the success of tumor therapy. In this current study, a multifunctional nanotheranostic agent of PDE-Ce6-HA was developed for tumor targeted and MRI-guided photodynamic/photothermal combined therapy (PDT/PTT). For this purpose, the near-infrared-absorbing nanoparticles of prussian blue were coated with polydopamine and successively conjugated with chlorin e6 (Ce6) for reactive oxygen species (ROS) generation. The resultant nanoparticles, denoted as PDE-Ce6, were then modified with hyaluronic acid (HA) through electrostatic interaction to yield the final therapeutic agent of PDE-Ce6-HA NPs. PDE-Ce6-HA NPs not only exhibited high colloid stability, good biocompatibility and suitable transverse relaxation rate (0.54 mM −1 s −1 ), but also high photothermal conversion efficiency (40.4%) and excellent ROS generation efficiency under NIR light irradiation. The confocal microscopy images demonstrated a selective uptake of PDE-Ce6-HA by CD44 overexpressed HeLa cells via HA-mediated endocytosis. Meanwhile, in vitro anti-cancer evaluation verified the significant photodynamic and photothermal combined effects of PDE-Ce6-HA on cancer cells. Moreover, PDE-Ce6-HA led to an increase of T 1 -MRI contrast in tumor site. Furthermore, in vivo anti-tumor evaluation proved that the PDE-Ce6-HA under both 808 and 670 nm laser showed significantly high tumor growth inhibition effects compared with individual PTT or PDT. Hence, PDE-Ce6-HA is applicable in tumor targeted and MRI-guided photodynamic/photothermal combined treatment.

Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

AbstractThe association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV− groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV− group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV− group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

Effects of long-acting versus short-acting granulocyte colony stimulating factor after radiotherapy in gynecologic malignancies: a prospective observational cohort study

Little is known about the role of the protective effects of granulocyte colony-stimulating factor (G-CSF) in patients after radiotherapy. The aim of the present study was to explore the prophylactic effects of long-acting granulocyte colony-stimulating factor (G-CSF) on febrile neutropenia (FN) and myelosuppression in chemotherapy patients with gynecologic malignancies after pelvic radiotherapy. Patients voluntarily participated in a study group (long-acting G-CSF for all chemotherapy cycles) and a control group (short-acting G-CSF) after they were educated about G-CSF utilization. The incidences of FN and myelosuppression, as well as adverse events, were compared between the two groups. A regression model was used to determine the risk factors for FN and myelosuppression. From January 6, 2019, to August 22, 2019, 61 patients were included in the final analysis, with 286 chemotherapy cycles. There were 14 (23.0%) and 57 (77.0%) patients in the study and control groups, respectively. The study group had significantly fewer complete blood count tests, fewer outpatient clinic visits, fewer short-acting G-CSF doses, and lower incidences of FN and myelosuppression per chemotherapy cycle. According to the binary regression model, the use of long-acting G-CSF was the only factor associated with a decreased incidence of myelosuppression but not FN. The major adverse event related to G-CSF was mild bone pain. In conclusion, long-acting G-CSF may effectively reduce the incidence of FN and myelosuppression with mild adverse effects during chemotherapy after radiotherapy.Trial registrationRegistered at https://www.clinicaltrials.gov/  on January 4, 2019 (NCT03793205).