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Transcriptomics and Cell Transformation Assay: an Integrated Approach to Evaluate the Effects of Low Dose Ionizing Radiation 转录组学和细胞转化试验:一种评估低剂量电离辐射影响的综合方法
Pub Date : 2021-07-23 DOI: 10.51626/ijor.2021.02.00005
Background and aims: Ionizing radiation (IR) are a well-known carcinogenic agent, acting through genotoxic mechanisms. In the last years, great attention has been paid to the effects of IR at low doses and to the non-monotonic dose-response curve for IR exposures. To improve the knowledge of IR-mediated effects and possibly identify biomarkers for IR effects, we combined the Cell Transformation Assay (CTA) with transcriptomics, to correlate cytotoxicity and transformation endpoints with the modulation of gene profiles after IR exposure.Methods: BALB/c3T3 cells were exposed to ionizing radiation ranging from 0.25Gy and 6Gy. Irradiated cells were seeded for the CTA 20h later. At the same time, RNA was extracted for microarray experiments. The cell clonal survival was significantly increased in 0.25Gy IR exposed cells, while the 3Gy dose strongly inhibited cellular growth. Cell transformation was observed only at the highest dose (3Gy).Results: Cell’s transformation was observed at 1.5, 2 and 3Gy doses. The 0.25Gy dose, which was able to induce an increment of clonal efficiency, did not induce cell transformation. The gene expression profile, which was obtained by comparing cells treated with the highest tested dose of 3Gy with the cells exposed to the lowest, not transforming, dose of 0.25Gy, identified several genes related to mitotic cell cycle and cholesterol biosynthesis. Conclusion: Our study showed that the up-regulation of genes belonging to the Spindle Assembly Checkpoint and mitosis progression could support the transforming ability of the 3Gy BALB/c3T3 exposed cells, probably through the involvement of genomic instability. Gene transcripts involved into cholesterol biosynthesis appear to be critical, as well. All these transcripts may be regarded as potential biomarkers of IR effects.
背景与目的:电离辐射(IR)是一种众所周知的致癌物质,通过遗传毒性机制起作用。近年来,人们对低剂量辐照的影响和辐照的非单调剂量-反应曲线给予了极大的关注。为了提高对IR介导效应的认识,并可能识别IR效应的生物标志物,我们将细胞转化试验(CTA)与转录组学相结合,将细胞毒性和转化终点与IR暴露后基因谱的调节联系起来。方法:BALB/c3T3细胞暴露于0.25Gy ~ 6Gy的电离辐射下。照射后的细胞于20h后接种CTA。同时提取RNA进行微阵列实验。0.25Gy辐照组细胞克隆存活率显著提高,3Gy辐照组细胞生长受到明显抑制。仅在最高剂量(3Gy)下观察到细胞转化。结果:在1.5、2、3Gy剂量下观察到细胞的转化。0.25Gy剂量虽能提高克隆效率,但未诱导细胞转化。通过比较接受最高剂量3Gy照射的细胞和接受最低剂量(不转化)0.25Gy照射的细胞获得的基因表达谱,鉴定出了几个与有丝分裂细胞周期和胆固醇生物合成相关的基因。结论:我们的研究表明,纺锤体组装检查点基因的上调和有丝分裂进程可能通过参与基因组不稳定性来支持3Gy BALB/c3T3暴露细胞的转化能力。参与胆固醇生物合成的基因转录物似乎也很关键。所有这些转录本都可能被视为IR效应的潜在生物标志物。
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引用次数: 1
Follicular Lymphoma Involving Bilateral Ovaries Following Routine Hysterectomy and Bilateral Salpingo-Oophorectomy: An Incidental Finding 常规子宫切除术及双侧输卵管卵巢切除术后发生双侧卵巢滤泡性淋巴瘤:偶然发现
Pub Date : 2020-12-14 DOI: 10.20944/preprints202012.0347.v1
Anoshia Afzal, M. Quinton, U. Farooque, S. Asadbeigi, B. Khan, S. Khan
Ovarian lymphoma is an infrequent disease, accounting for less than 1% of all non-Hodgkin lymphoma diagnosis. Symptoms include abnormal vaginal bleeding or discharge, abdominal pain, and urinary obstruction due to the large mass. In our case, a 60-year-old woman, underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy, as she presented with low-grade follicular lymphoma (FL) in both the ovaries, and the left ovary was observed to be enlarged. The tumor is categorized as lymphoma based upon immunohistochemical markers. Computed tomography (CT) scan of the chest, abdomen, and pelvis and bone marrow biopsy are important for the staging of primary lymphoma of the ovary. The first-line chemotherapy regimen includes rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (R-CHOP) for rapidly proliferative non-Hodgkin lymphoma (NHL). Lymphomas with slower growth patterns can be treated with Bendamustine-Rituximab and don’t need aggressive R-CHOP treatment.
卵巢淋巴瘤是一种罕见的疾病,占所有非霍奇金淋巴瘤诊断的不到1%。症状包括阴道异常出血或分泌物,腹痛,以及由大肿块引起的尿路梗阻。在我们的病例中,一名60岁的女性,由于双侧卵巢出现低级别滤泡性淋巴瘤(FL),左侧卵巢肿大,接受了全腹部子宫切除术和双侧输卵管卵巢切除术。根据免疫组织化学标记物将肿瘤分类为淋巴瘤。胸部、腹部、骨盆的计算机断层扫描(CT)和骨髓活检对卵巢原发性淋巴瘤的分期很重要。一线化疗方案包括利妥昔单抗、环磷酰胺、盐酸多柔比星(hydroxydaunorubicin)、硫酸长春新碱(Oncovin)和强的松(R-CHOP)治疗快速增殖性非霍奇金淋巴瘤(NHL)。生长模式较慢的淋巴瘤可以用苯达莫司汀-利妥昔单抗治疗,不需要积极的R-CHOP治疗。
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引用次数: 0
Glioblastoma Re-Irradiation: Impact of Concomitant Bevacizumab - Retrospective Series of 61 Cases 胶质母细胞瘤再照射:伴随贝伐单抗的影响——61例回顾性分析
Pub Date : 2020-12-12 DOI: 10.51626/ijor.2020.01.00001
Purpose: Glioblastoma is the most common primary brain tumor with a poor prognosis. Although the standard of initial treatment is well defined, no recommendation exists in the relapse setting. This work focuses on the optimal strategy for recurrent glioblastoma.Methods: We performed a retrospective monocentric analysis of all recurrent glioblastoma adult patients treated since 2000 in one neuro-oncology center by re-irradiation, alone or combined with chemotherapy and/or surgery at first or second relapse.Results: Overall, 61 patients underwent a re-irradiation for glioblastoma relapse. Patient median age at diagnosis was 55 (27 to 76), 44% were women. At diagnosis, 77% underwent surgical resection and 23% were biopsied. Most of them (95%) received a Stuppregimen. After a median follow-up of 31.1 months, 44 patients (72%) had died and the median overall survival (mOS) was 39.8 months. Regardless of the time of treatment (first or second relapse), patients treated with radiation therapy concomitant to bevacizumab (RTbev, n=36) showed superior survival data compared to patients treated with radiation therapy alone (RTalone, n=17). At first relapse, median progression free survival (mPFS) of RTbev (n=19) was 9.9 versus 3.6 months for RTalone (n=6) (OR=3.98 (3.14-61.81); p=0.001). At second relapse, mPFS of RTbev (n=17) was 9.2 versus 5.4 months for RTalone (n=11) (OR=2.31 (1.18-7.75); p =0.03), and mOS of RTbev was 15.2 versus 9.1 months for RTalone (OR=3.60 (2.17-18.13); p=0.001).Conclusion: This retrospective monocentric analysis reports a favorable impact of bevacizumab adjunction to re-irradiation. The high mOS may be due to patient selection, but emphasis the relevance of a multidisciplinary approach.
目的:胶质母细胞瘤是最常见的原发性脑肿瘤,预后较差。虽然初始治疗的标准是明确的,但在复发的情况下没有建议。这项工作的重点是复发性胶质母细胞瘤的最佳策略。方法:我们对自2000年以来在一个神经肿瘤中心接受再照射、单独或联合化疗和/或手术治疗的所有复发性胶质母细胞瘤成人患者进行了回顾性单中心分析。结果:总体而言,61例胶质母细胞瘤复发患者接受了再次放疗。患者诊断时的中位年龄为55岁(27 - 76岁),44%为女性。确诊时,77%接受手术切除,23%接受活检。他们中的大多数(95%)接受了Stuppregimen。中位随访31.1个月后,44例(72%)患者死亡,中位总生存期(mOS)为39.8个月。无论治疗时间(第一次或第二次复发),与单独放疗(RTalone, n=17)的患者相比,放疗联合贝伐单抗治疗的患者(RTbev, n=36)显示出更高的生存数据。首次复发时,RTbev (n=19)的中位无进展生存期(mPFS)为9.9个月,而RTalone (n=6)为3.6个月(OR=3.98 (3.14-61.81);p = 0.001)。第二次复发时,RTbev (n=17)的mPFS为9.2个月,而RTalone (n=11)的mPFS为5.4个月(OR=2.31 (1.18-7.75);p =0.03), RTbev的生存期为15.2个月,RTalone的生存期为9.1个月(OR=3.60 (2.17-18.13);p = 0.001)。结论:本回顾性单中心分析报告了贝伐单抗配合再照射的有利影响。高mOS可能是由于患者选择,但强调多学科方法的相关性。
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引用次数: 0
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International Journal on Oncology and Radiotherapy
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