Effectiveness of intraoperative radiotherapy vs hypofractionated postmastectomy radiotherapy for early stage breast cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Radiotherapy is one of the essential components of breast cancer treatment. It destroys the remaining cells in the chest area after breast cancer surgery and is useful for reducing the necessity of mastectomies. As a single dose of radiation at the time of breast conserving surgery, intraoperative radiotherapy delivers radiotherapy directly and accurately to the tumor itself or the tumor bed whilst delivering minimal dose to the surrounding normal tissues. Hypofractionated postmastectomy radiotherapy with shorter and more convenient hypofractionated dose schedules might help to treat more patients and reduce cost. We will conduct a comprehensive systematic review and meta-analysis to compare the effectiveness of these 2 therapies in the management of early stage breast cancer. METHODS: Four English databases (PubMed, Embase, Cochrane Library, and Web of Science) and 3 Chinese databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) will be searched from inception of databases to December 2020 without language limitation. Two reviewers will independently conduct selection of studies, data extraction and management, and assessment of risk of bias. Any disagreement will be resolved by the third reviewer. Review Manager 5.3 (The Cochrane Collaboration, Software Update, Oxford, UK) will be used for data synthesis. Cochrane risk of bias assessment tool will be used to assess the risk of bias. RESULTS: This study will provide a systematic synthesis of current published data to compare the effectiveness of intraoperative radiotherapy vs hypofractionated postmastectomy radiotherapy for early stage breast cancer. CONCLUSIONS: This systematic review and meta-analysis will provide clinical evidence for the effectiveness of intraoperative radiotherapy vs hypofractionated postmastectomy radiotherapy for early stage breast cancer, and inform our understanding of the value of intraoperative radiotherapy and hypofractionated postmastectomy radiotherapy for early stage breast cancer. STUDY REGISTRATION NUMBER: INPLASY2020110115.

Low-grade slightly elevated and polypoid colorectal adenomas display differential ß-catenin-TCF/LEF activity, c-Myc, and cyclin D1 expression.

AIM: To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas. METHODS: Colorectal tumors were collected from 24 patients with slightly elevated adenomas and 23 patients with polypoid adenomas. Five commonly mutated genes (APC, BRAF, KRAS, NRAS, and PIK3CA) were selected for mutational analysis. Paraffin-embedded tumor sections were used to calculate the apoptotic index (AI) and Ki-67 labeling index (KLI). Two pure colorectal epithelial cell lines were created by pooling the slightly elevated and polypoid tumors. Western blots, luciferase assays for ß-catenin-T-cell factor protein/ß-catenin-lymphoid enhancer factor (ß-catenin-TCF/LEF)-driven transcriptional activity, and caspase activity assays were conducted on the two cell lines. RESULTS: Slightly elevated lesions showed a significantly lower APC mutational frequency and a significantly higher KRAS mutational frequency (both P < 0.05). Slightly elevated lesions showed a significantly lower AI (P < 0.05). ß-catenin and ß-catenin-TCF/LEF-driven transcriptional activity was significantly upregulated in slightly elevated lesions (both P < 0.05). In slightly elevated lesions, c-Myc was significantly downregulated, while cyclin D1 was significantly upregulated (both P < 0.05). ß-catenin-TCF/LEF-driven transcriptional activity was negatively correlated with c-Myc (ρ = -0.78). Slightly elevated lesions displayed significant Bcl-2 and Bcl-xL upregulation (both P < 0.05) along with significant decreases in caspase-9 and caspase-3 activity (both P < 0.05). c-Myc was negatively correlated with Bcl-2 and Bcl-xL (ρ = -0.74 and -0.78, respectively). CONCLUSION: The lower apoptotic activity of low-grade slightly elevated adenomas can be partly attributed to upregulated ß-catenin pathway activity and downregulated c-Myc expression.