Guihao Ke

[Retracted] The Promotional Effect of Hollow MnO2 with Brucea Javanica Oil Emulsion (BJOE) on Endometrial Cancer Apoptosis

Endometrial cancer (EC) is a common gynecological malignancy worldwide whose therapy mainly depends on chemotherapy. In past years, an increasing number of studies indicate that hollow MnO2 could serve as a nanoplatform in the drug delivery system. The Brucea javanica oil emulsion (BJOE) has been illustrated to play a vital role in cancers. However, knowledge about the combined effect of H‐MnO2‐PEG/BJOE in endometrial cancer remains ambiguous up to now. In the present work, we prepared a drug‐delivery vector H‐MnO2‐PEG by chemical synthesis and found that H‐MnO2‐PEG significantly inhibited cell proliferation in endometrial cancer cells. Moreover, the combination of H‐MnO2‐PEG/BJOE could repress cell proliferation more efficiently and promote cell apoptosis. Mechanistically, we found that BJOE exerted its role as a promoter of endometrial apoptosis by regulating relative protein expressions. In general, the present study demonstrates that H‐MnO2‐PEG functions as a critical vector in the tumor microenvironment of endometrial cancer and the significant effect of H‐MnO2‐PEG/BJOE on cancer cells, suggesting a new paradigm for the treatment of endometrial cancer.

Overexpressed CD24 and CD47 Indicate a Worse Prognosis in Cervical Cancer

ABSTRACT Background Two antiphagocytic (“don't eat me”) signals that allow tumor immune evasion have been discovered, including CD24 and CD47. This study explored the association between CD24/CD47 expression and macrophage infiltration and clinical outcomes in cervical cancer. Methods RNA expression and survival data of the Cancer Genome Atlas (TCGA) cohort were extracted from OncoLnc. The macrophage infiltration level was calculated using xCell, TIMER, and ImmuCellAI. The expression of CD24 and CD47 was detected by immunohistochemistry in tissue microarrays composed of 130 clinical cervical cancer specimens from Fudan University Shanghai Cancer Center (FUSCC). Patients' medical records were also retrospectively assessed to correlate demographic and survival data. Results Expression levels of both CD24 and CD47 in the cancer population were higher than those in the normal population. Patients with high CD24 expression had poorer survival than those with low CD24 expression in the TCGA and FUSCC cervical cancer cohorts. Although CD47 alone was not statistically significant in predicting outcomes, patients with high CD47 and low CD11c expression, a specific marker of M1‐polarized macrophages, exhibited worse survival in the TCGA cohort. Conclusions Our study implies that high CD24 expression is an important predictor of a worse prognosis, and CD24 blockade might have therapeutic potential for the treatment of cervical cancer. High expression levels of CD47 and low M1‐polarized macrophage infiltration predict a worse prognosis.

Clinicopathologic and survival analysis of patients with adenoid cystic carcinoma of vulva: single-institution experience

The purpose of this study was to elucidate our experience in the diagnosis and treatment of adenoid cystic carcinoma of the vulva (ACC-vulva) and to assess the clinicopathological characteristics and prognosis among ACC-vulva patients. A retrospective study of seventeen patients was performed to illustrate the demographic information, clinical performance, pathological characteristics, treatment modality, and development of local recurrence or distant metastasis, as well as the survival outcome. The median age at diagnosis was 56 years (range, 26-71 years). Radical local excision was performed on fifteen patients, and two patient received radical hemi-vulvectomy. Six patients received ipsilateral inguinal lymphadenectomy. Involvement of the resection margin was observed in six patients. The postoperative pathologic diagnosis showed no proof of inguinal lymph node metastasis in all the six patients receiving lymphadenectomy. However, the perineural invasion was observed in all patients. Postoperative adjuvant radiotherapy was applied to five patients who had positive resection margin. The mean survival time except for that in four patients (recent case) was 47.8 months (range, 23-78 months). Radical resection towards negative margins seems to be acceptable as initial treatment. Adjuvant radiotherapy is a preferable treatment modality for patients with high-risk factors pathologically or patients with local recurrence.

BRD4 inhibition sensitizes cervical cancer to radiotherapy by attenuating DNA repair

Cisplatin-based chemoradiotherapy is the recommended treatment for local advanced cervical cancer, but radioresistance remains one of the most important and unresolved clinical problems. Investigations have revealed aberrant epigenetic modifications as one of the chief culprits for the development of radioresistance. Here, we attempt to identify a radiosensitizer from an epigenetic drug synergy screen and explore the underlying mechanism. We integrated epigenetic inhibitors and radiotherapy in cervical cancer cell lines to identify potential radiosensitizers. We further verified the sensitization effect of the drug and the function of its target gene both in vitro and in vivo. Finally, we validated the clinical significance of its target gene in clinical cervical cancer specimens. We identified JQ1, a BRD4 inhibitor, as a potent radiosensitizer. Functional assays demonstrated that repressing BRD4 activity led to significant radiosensitization and potentiation of DNA damage in cervical cancer cell lines. By using RNA-seq to determine JQ1-mediated changes in transcription, we identified RAD51AP1 as a major BRD4 target gene involved in radiosensitivity. A dual-luciferase reporter assay and ChIP-qPCR showed that BRD4 binds to the promoter region of RAD51AP1 and promotes its transcription, whereas this activity was attenuated by BRD4 inhibition. The in vivo experiments also suggested a synergy between BRD4 inhibition and radiotherapy. High BRD4 expression was found to be related to a worse prognosis and radiation resistance. BRD4 inhibition sensitizes cervical cancer to radiotherapy by inhibiting RAD51AP1 transcription. The combination of JQ1 with radiotherapy merits further evaluation as a therapeutic strategy for improving local control in cervical cancer.

Clinical Implication of Simultaneous Intensity-modulated Radiotherapy Boost to Tumor Bed for Cervical Cancer with Full-thickness Stromal Invasion

Abstract Objective The objective of this study was to retrospectively explore the clinical implications of simultaneous intensity-modulated radiotherapy (IMRT) boost to the tumor bed in cervical cancer with full-thickness stromal invasion (FTSI). Patients and Methods Patients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB and IIA cervical cancer with confirmed FTSI were included. Patients received pelvic IMRT from a dose of 50.4 Gy in 28 fractions with (or without) a simultaneous integrated boost (SIB) to 58.8 Gy in 28 fractions for the tumor bed. The progression-free survival (PFS), overall survival (OS), and pelvic-PFS (p-PFS) were analyzed using the Kaplan–Meier method, and independent prognostic factors were explored by Cox regression analyses. Results Patients without a tumor bed boost had a poor prognosis. The 5-year OS was 81.3% versus 58.3% and the 5-year PFS rates were 75.0% versus 57.6% (boost vs non-boost). The FIGO stage, pathology, adjuvant chemotherapy, and tumor bed boost were independent factors affecting both the 5-year OS and PFS. Subgroup analysis showed that the SIB group had a higher 5-year OS, PFS, and p-PFS for different stages, lymph node status, and risk groups than the non-SIB group. Recurrence occurred in 268 of 910 (29.5%) patients without SIB and 49 of 293 (16.7%) with SIB. Among patients with recurrence, 113 of 282 (40.1%) in the non-boost group compared with 14 of 51 (23.0%) patients in the boost group had a pelvic recurrence. Tumor bed boost resulted in an increase in the mean radiation dose to the intestine, rectum, and bladder, although there were no differences in the rates of acute and late toxicities between the 2 groups. Conclusion Tumor bed boost by external beam radiotherapy (EBRT) is an effective and safe method for patients with FTSI and risk factors. Compared with the standard prophylactic radiation, tumor bed boost by EBRT was not associated with increased acute and late toxicities.