Search

Abstract: Purpose: Quercetin (3, 3,′ 4′, 5, 7 – five-flavonoids) is one of the main components of flavonoids, with multifunctions on immune function, anti-oxidation, anti-viral, anti-inflammatory, and cardiovascular protection. We hypothesize that a combination of quercetin with radiation would increase tumor radiosensitivity. To test this hypothesis, we conducted in vitro and in vivo studies. Methods and materials: The in vitro radio-sensitization activity of quercetin was tested in DLD1, HeLa and MCF-7 tumor cell lines by colony formation assays. The in vivo activity was assessed in the DLD-1 human colorectal cancer xenograft model in nude mice. Mechanistic studies were conducted in several cell lines using Western blot analysis and immunofluorescence microscopy. Results: We found that quercetin can significantly increase tumor radiosensitivity both in vitro and in vivo. The in vitro Sensitizing Enhancement Ratios in DLD1, HeLa and MCF-7 cells were 1.87, 1.65, and 1.74, respectively. The mean doubling time of tumor xenografts was significantly increased in irradiated mice treated with quercetin. At the cellular level, exposure to quercetin resulted in prolonged DNA repair. The mechanistic studies demonstrated that quercetin induced radio-sensitization is through inhibiting the ATM kinase, one of the critical DNA damage response proteins. Conclusion: We demonstrate both in vitro and in vivo evidence that combination of quercetin with radiotherapy can enhance tumor radiosensitivity by targeting the ATM-mediated pathway in response to radiation. [Copyright &y& Elsevier]

Abstract: Purpose: Providing adequate dosimetric coverage of elongated, curvilinear incisions during adjuvant intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) creates technical challenges. We explored high-dose-rate (HDR) surface brachytherapy to supplement dose to multiple curvilinear incisions. This modality circumvents the technical limitations of relying on multiple en face electron fields while minimizing dose to adjacent normal tissues. Methods and Materials: A 59-year-old man presented with a left-sided, Stage III, T3N2M0, epithelioid MPM. After undergoing a left EPP, adjuvant IMRT was recommended to improve local control. An eight-field IMRT plan was designed to encompass the postoperative hemithorax. Incisional scars were lengthy and extended beyond the hemithoracic target volume. Both en face electron and surface HDR plans were prepared and evaluated based on dosimetric coverage of the incisional scars, dose to normal tissues, reliability of setup, and treatment delivery. Results: HDR was preferred. The patient was planned and treated in the right lateral decubitus position. HDR source catheters were placed along the incisions atop 5-mm bolus. A composite plan including IMRT and brachytherapy dose contributions was produced. Boosts of incisional scars were performed in six fractions (three fractions per week) of 3Gy prescribed to 12mm from the catheter. HDR brachytherapy was well tolerated. Conclusions: Surface HDR brachytherapy is a viable option for supplemental dose to incisional scars at risk of local recurrence after EPP for MPM. Advantages over electron beam therapy include avoidance of field abutments and feathering, less tissue–bone interface dose uncertainty and reproducibility of treatment delivery. [Copyright &y& Elsevier]