Purpose: Laryngeal carcinomas always resist to radiotherapy. Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngeal carcinoma. Methods: We assessed the effect of GLUT-1 expression on radioresistance of laryngeal carcinoma and the effect of GLUT-1 expressions by antisense oligodeoxynucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vitro and in vivo. Results: After transfection of GLUT-1 AS-ODNs: MTS assay showed the survival rates of radiation groups were reduced with the prolongation of culture time (p<0.05); Cell survival rates were significantly reduced along with the increasing of radiation dose (p<0.05). There was significant difference in the expression of GLUT-1mRNA and protein in the same X-ray dose between before and after X-ray radiation (p<0.05). In vivo, the expressions of GLUT-1 mRNA and protein after 8Gy radiation plus transfection of GLUT-1 AS-ODNs were significant decreased compared to 8Gy radiation alone (p<0.001). Conclusion: Radioresistance of laryngeal carcinoma may be associated with increased expression of GLUT-1 mRNA and protein. GLUT-1 AS-ODNs may enhance the radiosensitivity of laryngeal carcinoma mainly by inhibiting the expression of GLUT-1.
BackgroundThe efficacy of prophylactic cranial irradiation (PCI) in treating patients with small cell lung cancer (SCLC) has not been clear, and recent randomized studies have demonstrated conflicting results from previously published findings. The purpose of this study was to reevaluate the efficacy of PCI in patients with SCLC and to assess factors associated with its efficacy.MethodsWe conducted a quantitative meta-analysis to explore the efficacy of PCI in patients with SCLC. A literature search was performed using EMBASE, MEDLINE, Cochrane and ClinicalTrials.gov databases. We pooled the data and compared overall survival (OS) and brain metastasis (BM) between patients treated with PCI (PCI group) and patients without PCI treatment (observation group).ResultsOf the 1074 studies identified in our analysis, we selected seven studies including 2114 patients for the current meta-analysis. Our results showed that the PCI group showed decreased BM (HR = 0.45, 95% CI: 0.38–0.55, P < 0.001) and prolonged OS (HR = 0.81, 95% CI: 0.67–0.99, P < 0.001). However, in terms of OS, the pooled analysis showed a high heterogeneity (I2 = 74.1%, P = 0.001). In subgroup analyses of OS, we found that the heterogeneity mainly came from patients with brain imaging after initial chemoradiotherapy (HR = 0.94, 95% CI: 0.74–1.18, P = 0.59).ConclusionsThe results of this study showed that PCI has a significant effect on decreasing BM but little benefit in prolonging OS when brain imaging was introduced to confirm lack of BM after initial chemoradiotherapy and before irradiation.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-5251-3) contains supplementary material, which is available to authorized users.
BackgroundDeep inspiration breath hold (DIBH) can be performed using different breathing maneuvers, such as DIBH with a thoracic breathing maneuver (T-DIBH) and DIBH with an abdominal breathing maneuver (A-DIBH). Dosimetric benefits of A-DIBH were investigated in the treatment of left-sided breast cancer radiotherapy (RT) with both 3-Dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques.MethodsTwenty-two patients with left-sided breast cancer were enrolled in this study. 3D-CRT and IMRT plans were generated for each patient with three different CT scans of free breathing (FB), T-DIBH and A-DIBH. There were total of six treatment plans generated for each patient: FB_3D-CRT; TDIBH_3D-CRT; ADIBH_3D-CRT; FB-IMRT; TDIBH-IMRT; ADIBH-IMRT. Doses to the heart, left anterior descending coronary artery (LADCA), and ipsilateral lung were evaluated and compared using the Wilcoxon signed-rank test.ResultsThe mean doses to the heart, LADCA and ipsilateral lung in 3D-CRT plans generated from 3D-CRT with FB, T-DIBH and A-DIBH were (2.89 ± 1.30), (1.67 ± 0.90) and (1.34 ± 0.43) Gy (all P < 0.05), respectively, with FB; (29.08 ± 16.72), (13.94 ± 14.74) and (10.22 ± 10.30) Gy (all P < 0.05), respectively, with T-DIBH; and (7.77 ± 2.71), (7.32 ± 1.42) and (6.90 ± 1.60) Gy (all P < 0.05), respectively, with A-DIBH. The mean doses to the heart, LADCA and ipsilateral lung in IMRT plans were generated from IMRT with FB, T-DIBH and A-DIBH were (1.96 ± 2.25), (1.37 ± 0.44) and (1.18 ± 0.26) Gy (all P < 0.05), respectively, with FB; (16.10 ± 7.45), (8.6 ± 6.60) and (7.35 ± 5.42) Gy (all P < 0.05), respectively, with T-DIBH; and (5.90 ± 2.24), (5.65 ± 1.58) and (5.62 ± 1.05) Gy (all P > 0.05), respectively, with A-DIBH.ConclusionsThis study indicates that both 3D-CRT and IMRT plans with A-DIBH achieved lower cardiac and LADCA doses than plans with FB and T-DIBH; 3D-CRT plans with A-DIBH achieved lower ipsilateral lung doses than plans with FB and T-DIBH; and IMRT plans with A-DIBH had better outcomes than 3D-CRT plans with A-DIBH with respect to the mean dose to the heart, LADCA and ipsilateral lung. IMRT plans with A-DIBH should be incorporated into the daily routine for left-sided breast RT.
The delivery of high dose radiotherapy to tumors is often limited by the proximity of the surrounding radiosensitive normal tissues, even using modern techniques such as intensity modulated radiation therapy (IMRT). Previous studies have reported that placement of a spacer can effectively displace normal tissues. So that they are some distance away from the lesion, thus allowing for the safe delivery of high-dose radiation. The application of radioprotective spacers was first reported 30 years ago regarding radiotherapy of tongue and abdominal cancers; more recently, they are increasingly being used in prostate cancer. This review focuses on the published data concerning the features of different types of spacers and their application in various tumor sites. Placement-related complications and the cost-effectiveness of the spacers are also discussed. With the increasing use of high-precision radiotherapy in clinical practice, especially the paradigm-changing stereotactic body radiotherapy (SBRT), more robust studies are warranted to further establish the role of radioprotective spacers through materials development and novel placement techniques.
The mechanisms underlying cancer radioresistance remain unclear. Several studies have found that increased glucose transporter‑1 (GLUT‑1) expression is associated with radioresistance. Recently, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway was reported to be involved in the control of GLUT‑1 trafficking and activity. Activation of the PI3K/Akt pathway may itself be associated with cancer radioresistance. Thus, increasing attention has been devoted to the effects of modifying the expression of GLUT‑1 and the PI3K/Akt pathway on the increase in the radiosensitivity of cancer cells. This review discusses the importance of the association between elevated expression of GLUT‑1 and activation of the PI3K/Akt pathway in the development of radioresistance in cancer.
BackgroundBone is a preferential site for prostate cancer (PCa) metastasis. However, sites of synchronous distant metastases in PCa patients with bone metastases at initial diagnosis and their impacts on prognosis are still unclear, limiting our ability to better stratify and treat the patients. In this study, we examined the sites of synchronous extra‐skeletal metastases in de novo PCa patients with bone metastases and their associated prognoses. MethodsIn total, 16,643 de novo PCa patients with bone metastases from the SEER database were included. After stratification of metastatic sites (bone, lung, liver, and brain) and treatment modalities, overall survival (OS) and independent predictors of OS, were analyzed. ResultsLung was the most frequent site of synchronous metastases, followed by liver, while brain metastases were relatively uncommon. Patients with bone‐only metastases showed the longest mean survival time (35.87 months, p < 0.001), followed by patients with bone and lung metastases (30.74 months, p < 0.001). Patients with bone and liver metastases had the shortest mean survival time (17.39 months, p < 0.001). Age > 70 years, unmarried status, high tumor grade, prostate‐specific antigen (PSA) > 50 ng/ml, and Gleason score ≥ 8 were associated with poor OS (all p < 0.01). Asian or Pacific Islander ethnic background was associated with a favorable OS (all p < 0.01). Chemotherapy improved OS in patients without brain metastases (all p < 0.05). For patients with bone‐only metastases, radical prostatectomy (RP) (HR, 0.339; 95% CI 0.231–0.495; p < 0.001), brachytherapy (BT) (HR, 0.567; 95% CI 0.388–0.829; p = 0.003), and chemotherapy (HR, 0.850; 95% CI 0.781–0.924; p < 0.001) were associated with prolonged OS. ConclusionsAge, race, tumor grade, PSA, Gleason score, sites of synchronous extra‐skeletal metastases, as well as treatment modalities affected OS in newly diagnosed PCa patients with bone metastases. Synchronous liver metastases were associated with poor OS. Chemotherapy improved OS in patients without brain metastases. RP and BT improved OS in patients with bone‐only metastases. Further investigation is warranted to validate these findings.
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