International Journal of Radiation Biology

High HPV viral load predicts worse prognosis in patients with cervical cancer treated with radiochemotherapy

To evaluate the prognostic value of high-risk human papillomavirus (HR-HPV) viral load in long-term survival of cervical cancer (CC) patients. Two hundred and twenty-nine CC patients from 2009 to 2013 who underwent radiochemotherapy (RCT) or plus hyperthermia (HT) were recruited. HPV type 16, 18, 58 DNA was detected by in situ hybridization (ISH) and either HR-HPV type with the highest intensive signals was chosen as the evaluating target. HPV viral load was evaluated by semiquantitative analysis for the intensity of ISH signal captured from the colonial cancer nests with the highest density of signal on section from each case. RNA scope was used to detect the HPV E6/E7 mRNA and P53/Rb mRNA expression. Immunohistochemistry (IHC) was used to detect P53/Rb protein expression. The number of patients with low and high HPV viral load was 152 (66.38%) and 77 (33.62%), respectively. 5-year Overall Survival (OS) of patients in the low and high HPV DNA group were 82.9 and 63.6%, respectively ( High initial viral load measured in cervical tumor nest was a strong independent prognostic factor that influenced poor survival in CC after RCT.

Activation of COL11A1 by PRRX1 promotes tumor progression and radioresistance in ovarian cancer

Although radiotherapy is a common treatment option for all kinds of cancer patients, including ovarian cancer, a major obstacle limiting its application in the development of resistance. Therefore, it is urgently needed to clarify the mechanism of radiosensitivity modulation. We obtained open datasets and analyzed the expression of collagen type XI alpha 1 (COL11A1) in ovarian cancer patients with different stages. Meanwhile, the correlation of COL11A1 and survival outcomes is determined by Kaplan-Meier analysis. The role of COL11A1 in cell proliferation was observed in an in vitro knockdown system. SKOV3 radioresistant cells were established to determine the role of COL11A1 on radioresistant in ovarian cancer. COL11A1 were highly enriched in late-stage ovarian cancer tumor tissues and negatively correlated with survival outcomes in ovarian cancer. The functional analysis found that COL11A1 promoted ovarian cancer cell proliferation in vitro. Importantly, COL11A1 decreased radiosensitivity in ovarian cancer by AKT activation. Paired related homeobox 1 (PRRX1) acted as an upstream transcription factor to regulate COL11A1 expression in ovarian cancer. Increased COL11A1 expression is related to low survival outcomes and radiosensitivity in ovarian cancer. Targeting COL11A1 is a promising strategy for improving radiotherapy efficiency.

Noninvasive evaluation of HABP1 expression with 99m Tc-labeled small-interference RNA in ovarian cancer

Ovarian cancer is one of the most common gynecological cancers in women with a low 5-year survival rate. Evaluation of hyaluronic acid-binding protein 1 (HABP1) level can provide important information for the diagnosis and treatment of ovarian cancer. In this study, we designed a novel HABP1 probe based on A specific siHABP1 was selected because of its targetability and silencing effect. A negative control siRNA (NCsiRNA) with no homology with the human genome was used. SiHABP1 and NCsiRNA were radiolabeled with We showed that

Effect of low dose of berberine on the radioresistance of cervical cancer cells via a PI3K/HIF-1 pathway under nutrient-deprived conditions

Quality of radiation shapes survival, invasiveness, and migration in ovarian cancer cell lines with different molecular profiles and varying alpha/beta ratios: an in vitro study on behalf of the Multicenter Italian Trials in Ovarian Cancer (MITO) group

The results of radiotherapy (RT) in oligometastatic ovarian cancers (OCs) lead to the query whether it is possible to stratify patients based on tumor hallmarks to ensure the best-personalized RT treatment. To address this question, we designed a preclinical study to evaluate the effects of high and low linear energy transfer (LET) radiation while considering molecular features and alpha/beta ratios of different OC cell lines. Exponentially growing human OVSAHO, OVCAR8, COV362, and OVCAR3 cells cultured in T-25 and T-75 flasks were exposed to different single physical doses of photons, protons, and carbon ion (CIRT) irradiation. We assessed ovarian cells' in vitro response using clonogenic survival (fitted using LQ model), migration by Boyden chamber assay, and invasion through BioCoat Matrigel invasion assay. Following photon irradiation, OVCAR3 was the most radioresistant and OVCAR8 the most radiosensitive cell line. OC cell migration decreased in a dose-dependent manner after irradiation, with CIRT showing the strongest effect, evident by the α/β ratio. The number of invading cells decreased following irradiation with all types. However, the greatest reduction was seen in CIRT, particularly at higher α/β ratios. Proton irradiation demonstrated similar potential to photons but did not match the effects of carbon ions in terms of survival, migration, and invasion

Ultrasound-stimulated microbubbles enhances radiosensitivity in cervical cancer

Ultrasound-stimulated microbubble (USMB) therapy has proven efficacy of targeting tumor vasculature and enhancing the effect of radiation in tumor xenografts. In this investigation, we studied whether this treatment enhances the sensitivity of cervical cancer to radiation. Human cervical cancer (ME-180 and SiHa) cells were treated with USMB or exposed to radiation (0, 2, 4, 6 and 8 Gy) or radiation (8 Gy) in combination with USMB. Clone formation assay and CCK-8 assay were used to analyze the proliferation capacity of cells. Apoptosis and DNA double-strand breaks were detected using flow cytometry and immunofluorescence staining of gamma-H2AX (γ-H2AX), respectively. Matrigel tubule formation was performed to evaluate the angiogenesis of human umbilical vein endothelial cells. In xenograft model of SiHa cells, tumor tissue expression of CD31 was detected by immunohistochemistry. USMB and radiation synergistically restrained the growth of ME-180 and SiHa cells. USMB promoted radiation-induced apoptosis by enhancing the levels of proapoptotic proteins. Furthermore, USMB enhanced radiation-induced γ-H2AX foci to induce DNA double-strand breaks in cervical cancer cells. USMB in combination with radiation reduced the angiogenic capacity of endothelial cells in vitro. Moreover, USMB strengthened the inhibitory effect of radiation on tumor growth and angiogenesis in xenograft models. In conclusion, USMB exposure effectively enhanced the destructive effect of radiation on cervical cancer, suggesting that USMB might be a promising sensitizer of radiotherapy to treat cervical cancer.