RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Influence of Gender on Radiosensitivity during Radiochemotherapy of Advanced Rectal Cancer.
Influence of Gender on Radiosensitivity during Radiochemotherapy of Advanced Rectal Cancer.
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性别在医学中被越来越多地认为是一个重要因素,尽管在许多领域的医学研究中长期被忽视。我们研究了性别在晚期直肠癌中的影响,特别关注放射敏感性。为此,我们研究了一个队列,包括495名男性(84.1% ≥ T3,63.6% N1,17.6% M1)和215名女性(84.2% ≥ T3,56.7% N1,22.8% M1),他们均患有晚期直肠癌并接受了放化疗。评估了能量沉积、DNA双链断裂(dsb)修复、染色体畸变的发生、治疗持续时间、肿瘤消退和TIL(肿瘤浸润淋巴细胞)、实验室参数、生活质量和生存。照射后24小时淋巴细胞中残留的DNA dsb损伤在两性中相同。
此外,准确反映放射敏感性的染色体畸变在两性中相似。肿瘤消退、TIL(肿瘤浸润淋巴细胞)和结局没有性别依赖性差异,表明癌细胞的放射敏感性没有差异。女性受照射的肿瘤体积略低于男性,与体重相关,未观察到差异。
然而,当计算总能量沉积并与体重相关时,女性暴露于更高量的电离辐射。在放化疗期间,女性血液淋巴细胞计数和白蛋白的下降以及若干生活质量参数如恶心和呕吐、食欲丧失和腹泻显著更差。男性和女性在正常组织和肿瘤中的放射敏感性没有差异。在放化疗期间,女性的生活质量下降比男性更多。然而,女性也恢复得很快,生活质量没有长期差异。
Gender is increasingly recognized as an important factor in medicine, although it has long been neglected in medical research in many areas.
We have studied the influence of gender in advanced rectal cancer with a special focus on radiosensitivity. For this purpose, we studied a cohort of 495 men (84. 1% ≥ T3, 63. 6% N1, 17. 6%, M1) and 215 women (84. 2% ≥ T3, 56. 7% N1, 22. 8%, M1) who all suffered from advanced rectal cancer and were treated with radiochemotherapy.
The energy deposited, DNA double-strand break (dsb) repair, occurrence of chromosomal aberrations, duration of therapy, tumor regression and tumor-infiltrating lymphocytes, laboratory parameters, quality of life and survival were assessed. The residual DNA dsb damage 24 h after irradiation in lymphocytes was identical in both sexes.
Furthermore, chromosomal aberrations accurately reflecting radiosensitivity, were similar in both sexes. There were no gender-dependent differences in tumor regression, tumor-infiltrating lymphocytes and outcome indicating no differences in the radiosensitivity of cancer cells. The irradiated tumor volume in women was slightly lower than in men, related to body weight, no difference was observed.
However, when the total energy deposited was calculated and related to the body weight, women were exposed to higher amounts of ionizing radiation. During radiochemotherapy, decreases in blood lymphocyte counts and albumin and several quality-of-life parameters such as nausea and vomiting, loss of appetite, and diarrhea were significantly worse in women. There is no difference in radiation sensitivity between men and women in both normal tissue and tumors. During radiochemotherapy, the quality of life deteriorates more in women than in men.
However, women also recover quickly and there are no long-term differences in quality of life.
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