A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer.

OBJECTIVE: To study the effect of inhibitor of differentiation 3 (ID3) on radiotherapy in patients with rectal cancer and to explore its primary mechanism. METHODS: Cell proliferation and clonogenic assays were used to study the relationship between ID3 and radiosensitivity. Co-immunoprecipitation and immunofluorescence were performed to analyze the possible mechanism of ID3 in the radiosensitivity of colorectal cancer. At the same time, a xenograft tumor model of HCT116 cells in nude mice was established to study the effect of irradiation on the tumorigenesis of ID3 knockdown colorectal cancer cells in vivo. Immunohistochemistry was performed to analyze the relationship between ID3 expression and the efficacy of radiotherapy in 46 patients with rectal cancer. RESULTS: Proliferation and clonogenic assays revealed that the radiosensitivity of colorectal cancer cells decreased with ID3 depletion through p53-independent pathway. With the decrease in ID3 expression, MDC1 was downregulated. Furthermore, the expression of ID3, MDC1, and γH2AX increased and formed foci after irradiation. ID3 interacted with PPARγ and form a positive feedback loop to enhance the effect of ID3 on the radiosensitivity of colorectal cancer. Irradiation tests in nude mice also confirmed that HCT116 cells with ID3 knockdown were more affected by irradiation. Immunohistochemical study showed that rectal cancer patients with low expression of ID3 had better radiotherapy efficacy. CONCLUSIONS: ID3 and PPARγ influence the radiosensitivity of colorectal cancer cells by interacting with MDC1 to form a positive feedback loop that promotes DNA damage repair. Patients with low expression of ID3 who received neoadjuvant chemoradiotherapy can obtain a better curative effect.

[Study on the efficacy and complications of patients undergoing radical surgery and radical radiotherapy for localized prostate cancer].

OBJECTIVE: To compare the efficacy and complications of radical surgery (RP) and radical radiotherapy (RRT). METHODS: The clinical data of patients diagnosed with localized prostate cancer in General Hospital of Eastern Theater Command with RP and RRT from January 2015 to December 2019, Observed and recorded patient preoperative and postoperative PSA levels, biochemical Relapse-free Survival and clinical Relapse-free Survival,and the occurrence of hematuria, urinary incontinence, erectile dysfunction, ankylurethria, diarrhea, hemoproctia and radiocystitis. RESULTS: A total of 150 patients with localized prostate cancer were included in this study, including 105 patients with RP and 45 patients undergoing RRT. There was no significant difference between the complication rates of hematuria, urinary incontinence, erectile dysfunction and ankylurethria(P>0.05).Patients in the RRT group had higher rates of diarrhea(20.00% vs 2.86%), hemoproctia(15.56% vs 1.90%) and radiocystitis(13.33% vs 0%) than those in the RP group, with significant differences (P<0.05). The 5-year bRFS was lower than that in the RP group (95.1% vs 90.7%), with no statistical significance (P=0.832); the 5-year cRFS in the RP group was lower than that in the RRT group (91.2% vs 89.6%), with no significant difference (P=0.971). CONCLUSION: The incidence of diarrhea, hemoproctia and radiocystitis was lower in the RP group than in the RRT group, and the recurrence-free survival was not significantly different between the two groups.

Autophagy and Tumour Radiotherapy.

Radiotherapy is an important component of cancer treatment modalities. With the rapid development of three-dimensional conformal, intensity-modulated, image-guided radiotherapy and the efficacy of radiotherapy continues to improve. Autophagy, as a catabolic process, is characterized by the formation of a double-membrane vesicle. Radiotherapy is known to induce autophagy in both cancer and normal cells. Here, we reviewed the interaction of radiotherapy and autophagy in the process of cancer treatment. The potential role of autophagy modification in enhancing radiotherapy treatment will also be reviewed.

Prolyl hydroxylase domain 3 influences the radiotherapy efficacy of pancreatic cancer cells by targeting hypoxia-inducible factor-1α.

PURPOSE: Pancreatic cancer is characterized by a hypoxic microenvironment and resistance to most currently available treatment modalities. Prolyl hydroxylase domain 3 (PHD3) is a rate-limiting enzyme that regulates the degradation of hypoxia-inducible factors (HIFs) and is deregulated in pancreatic cancer cells. Whether such alteration of PHD3 expression contributes to the sustained growth and radioresistance of pancreatic cancer cells remains largely unknown. MATERIALS AND METHODS: PHD3 was overexpressed in pancreatic cancer Mia-paca2 cells via lentiviral expression. Cell cycle progression and apoptosis were assayed by flow cytometry. HIF-1α, EGFR, and PHD3 protein expression was assessed by Western blotting. Cell survival was determined in a colony formation assay. RESULTS: PHD3 overexpression suppressed HIF-1α protein expression and EGFR phosphorylation and enhanced the 2 Gy irradiation-mediated reductions in HIF-1α and phosphorylated (p)-EGFR under either normoxic or hypoxic conditions. PHD3 overexpression inhibited the growth and colony formation of Mia-paca2 cells in response to irradiation under either normoxic or hypoxic conditions. PHD3 overexpression exacerbated irradiation-induced apoptosis, with a greater effect under hypoxia than normoxia. Cell cycle distribution analysis demonstrated that PHD3 overexpression resulted in further shortened S phase and lengthened G2/M phase in response to irradiation. CONCLUSION: PHD3 expression may contribute to the radiotherapy efficacy of pancreatic cancer cells and serve as a novel biomarker for improving radiotherapy efficacy in pancreatic cancer.

Influence of autophagy on the efficacy of radiotherapy.

Autophagy is an important catabolic process in which cells digest and recycle their own cytoplasmic contents for maintaining cellular homeostasis. Interestingly, autophagy could play both pro-death and pro-survival roles in influencing the development of cancer via various signal pathways. As radiotherapy is one of the main treatment modalities for cancer, we reviewed the effect of autophagy modulations on radiosensitivity and radiotherapy efficacy in various cancer types. The future development of autophagy modifications for improving radiotherapy efficacy and cancer prognosis will also be discussed.