Background Ovarian cancer is the most common malignant tumor of the female reproductive tract. Chemoresistance is a major challenge for current ovarian cancer therapy. However, the mechanism underlying epithelial ovarian cancer (EOC) chemoresistance is not completely uncovered. The phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling is an important intracellular pathway in regulating cell cycle, quiescence, and proliferation. The aim of this study is to investigate the role of PI3K/Akt/mTOR signaling pathway and its association with epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) marker expression in EOC chemoresistance. Methods The expressions of EMT and CSC markers were detected by immunofluorescence, western blot, and quantitative real-time PCR. BEZ235, a dual PI3K/mTOR inhibitor, was employed to investigate the role of PI3K/Akt/ mTOR signaling in regulating EMT and CSC marker expression. Students’ t test and one-way ANOVA with Tukey’s post-hoc test were used to compare the data from different groups. Results We found that EMT and CSC marker expression were significantly enhanced in chemoresistant EOC cells, which was accompanied by the activation of PI3K/Akt/mTOR signaling. Compared with single cisplatin treatment, combined treatment with BEZ235 and cisplatin significantly disrupted the colony formation ability, induced higher ROS level and more apoptosis in chemoresistant EOC cells. Furthermore, the combination approach effectively inhibited PI3K/Akt/mTOR signaling pathway, reversed EMT, and decreased CSC marker expression in chemoresistant EOC cells compared with cisplatin mono-treatment. Conclusions Our results first demonstrate that EMT and enhanced CSC marker expression triggered by activated PI3K/Akt/mTOR signaling are involved in the chemoresistance of EOC, and BEZ235 in combination with cisplatin might be a promising treatment option to reverse EOC chemoresistance. Electronic supplementary material The online version of this article (10.1186/s12885-019-5824-9) contains supplementary material, which is available to authorized users.

Radiation therapy (RT) is one of the most important strategies in cancer treatment. Radioresistance (the failure to RT) results in locoregional recurrence and metastasis. Therefore, it is critically important to investigate the mechanisms leading to cancer radioresistance to overcome this problem and increase patients' survival. Currently, the majority of the radioresistance-associated researches have focused on preclinical studies. Although the exact mechanisms of cancer radioresistance have not been fully uncovered, accumulating evidence supports that cancer stem cells (CSCs) and different signaling pathways play important roles in regulating radiation response and radioresistance. Therefore, targeting CSCs or signaling pathway proteins may hold promise for developing novel combination modalities and overcoming radioresistance. The present review focuses on the key evidence of CSC markers and several important signaling pathways in cancer radioresistance and explores innovative approaches for future radiation treatment.

Chemoresistance is the main challenge for the recurrent ovarian cancer therapy and responsible for treatment failure and unfavorable clinical outcome. Understanding mechanisms of chemoresistance in ovarian cancer would help to predict disease progression, develop new therapies and personalize systemic therapy. In the last decade, accumulating evidence demonstrates that epithelial-mesenchymal transition and cancer stem cells play important roles in ovarian cancer chemoresistance and metastasis. Treatment of epithelial-mesenchymal transition and cancer stem cells holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. In this review, we focus on the role of epithelial-mesenchymal transition and cancer stem cells in ovarian cancer chemoresistance and explore the therapeutic implications for developing epithelial-mesenchymal transition and cancer stem cells associated therapies for future ovarian cancer treatment.

The most common ovarian cancer is epithelial ovarian cancer (EOC) characterised by few early symptoms, widespread peritoneal dissemination and ascites at advanced stages that result in poor prognosis. Despite the recent progress in its management, including surgery and chemotherapy, EOC remains the most lethal gynaecological malignancy in women. Due to the limitations of current therapeutic approaches, many patients die of secondary disease (metastasis). MUC1 is associated with cellular transformation and tumorigenicity and is considered as an attractive therapeutic target for cancer therapy owning to its over-expression in most adenocarcinomas including EOC. Tumour-associated MUC1 plays an important role in EOC metastasis and progression. In neoplastic tissues, MUC1 is underglycosylated and reveals epitopes that are masked in the normal cells. This feature makes it possible to target tumour-associated MUC1 with antibodies, toxins or radionuclides or use a vaccine targeting tumour-associated MUC1 antigen. The shed tumour-associated MUC1 in blood can be used as a diagnostic biomarker for EOC detection and monitoring. Our recent results have shown that over-expression of MUC1 plays a very important role in EOC progression and MUC1 is an ideal target for targeted therapy to control metastatic and recurrent EOC. This review will summarize some important new findings supporting the role of MUC1 in EOC metastasis and progression and focus on the MUC1-based targeted therapy for control of metastatic and recurrent EOC.

Purpose: This paper introduces a new external beam radiotherapy device named GammaPod that is dedicated for stereotactic radiotherapy of breast cancer. Methods:The design goal of the GammaPod as a dedicated system for treating breast cancer is the ability to deliver ablative doses with sharp gradients under stereotactic image guidance. Stereotactic localization of the breast is achieved by a vacuum-assisted breast immobilization cup with built-in stereotactic frame. Highly focused radiation is achieved at the isocenter due to the cross-firing from 36 radiation arcs generated by rotating 36 individual Cobalt-60 beams. The dedicated treatment planning system optimizes an optimal path of the focal spot using an optimization algorithm borrowed from computational geometry such that the target can be covered by 90%-95% of the prescription dose and the doses to surrounding tissues are minimized. The treatment plan is intended to be delivered with continuous motion of the treatment couch. In this paper the authors described in detail the gamma radiation unit, stereotactic localization of the breast, and the treatment planning system of the GammaPod system. Results: A prototype GammaPod system was installed at University of Maryland Medical Center and has gone through a thorough functional, geometric, and dosimetric testing. The mechanical and functional performances of the system all meet the functional specifications. Conclusions: An image-guided breast stereotactic radiotherapy device, named GammaPod, has been developed to deliver highly focused and localized doses to a target in the breast under stereotactic image guidance. It is envisioned that the GammaPod technology has the potential to significantly shorten radiation treatments and even eliminate surgery by ablating the tumor and sterilizing the tumor bed simultaneously.

Noise pollution has become a significant global problem in recent years. Unfortunately, conventional acoustic materials cannot offer substantial improvements in noise reduction. However, acoustic metamaterials are providing new solutions for controlling sound waves, and have huge potential for mitigating noise propagation in particular. Recently, owing to the rapid development of acoustic metamaterials, metamaterials for acoustic noise reduction have drawn the attention of researchers worldwide. These metamaterials are often both light and compact, and are excellent at reducing low‐frequency noise, which is difficult to control with conventional acoustic materials. Recent progress has illustrated that acoustic metamaterials effectively control sound waves, and optimizing their structure can enable functionality based on new physical phenomena. This review introduces the development of acoustic metamaterials, and summarizes the basic classification, underlying physical mechanism, application scenarios, and emerging research trends for both passive and active noise‐reduction metamaterials. Focusing on noise reduction, the shortcomings of current technologies are discussed, and future development trends are predicted. As our knowledge in this area continues to expand, it is expected that acoustic metamaterials will continue to improve and find more practical applications in emerging fields in the future.

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