A temperature-sensitive phase-change hydrogel of tamoxifen achieves the long-acting antitumor activation on breast cancer cells.

Background: Breast cancer is one of the foremost threats to female health nowadays. Tamoxifen, an antagonist of estrogen receptor-α (ERα), is the first choice for endocrine-dependent breast cancer (ERα-positive breast cancer) treatment. However, ERα has an important function in the normal physical regulation of estrogen, and current oral administration of tamoxifen has potential side effects on normal endocrine secretion. In the present work, we aim to develop novel approaches to increase the antitumor effect of tamoxifen on breast cancer cells and decrease the potential side effects in the human body during treatment. Methods: A temperature-sensitive phase-change hydrogel for tamoxifen (Tam-Gel) was generated. After establishing subcutaneous tumors formed by MCF-7, an ERα-positive breast cancer cell line, in nude mice, an intratumoral injection of Tam-Gel was performed to examine whether Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. A metastatic breast cancer model was established using the intrahepatic growth of MCF-7 cells in immunodeficient rats. Results: Tam-Gel can transform from liquid to hydrogel at room temperature. An intratumoral injection of Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. Once Tam-Gel, but not Tam-Sol, was administered by intratumoral injection, it significantly decreased the uptake of radionuclide probes (18F-fluoroestradiol or 18F-fluorodeoxyglucose) by cells in rats' livers and the intrahepatic growth of MCF-7 cells in rats' livers. Conclusion: A novel slow-release system was successfully prepared to facilitate the long-term release of tamoxifen in breast cancer tissues, and achieved an antitumor effect in the long term.

Dosimetric comparison of TomoDirect, helical tomotherapy, VMAT, and ff-IMRT for upper thoracic esophageal carcinoma.

BACKGROUND: The new TomoDirect (TD) modality offers a nonrotational option with discrete beam angles. We aim to compare dosimetric parameters of TD, helical tomotherapy (HT), volumetric-modulated arc therapy (VMAT), and fixed-field intensity-modulated radiotherapy (ff-IMRT) for upper thoracic esophageal carcinoma (EC). METHODS: Twenty patients with cT2-4N0-1M0 upper thoracic esophageal squamous cell carcinoma (ESCC) were enrolled. Four plans were generated using the same dose objectives for each patient: TD, HT, VMAT with a single arc, and ff-IMRT with 5 fields (5F). The prescribed doses were used to deliver 50.4 Gy/28F to the planning target volume (PTV50.4) and then provided a 9 Gy/5F boost to PTV59.4. Dose-volume histogram (DVH) statistics, dose uniformity, and dose homogeneity were analyzed to compare treatment plans. RESULTS: For PTV59.4, the D2, D98, Dmean, and V100% values in HT were significantly lower than other plans (all p < 0.05), and those in TD were significantly lower than VMAT and ff-IMRT (all p < 0.05). However, there was no significant difference in the D2 and Dmean values between VMAT and ff-IMRT techniques (p > 0.05). The homogeneity index (HI) differed significantly for the 4 techniques of TD, HT, VMAT, and ff-IMRT (0.03 ± 0.01, 0.02 ± 0.01, 0.06 ± 0.02, and 0.05 ± 0.01, respectively; p  < 0.001). The HI for TD was similar to HT (p = 0.166), and had statistically significant improvement compared to VMAT (p < 0.001) and ff-IMRT (p = 0.003). In comparison with the 4 conformity indices (CIs), there was no significant difference (p > 0.05). For PTV50.4, the D2 and Dmean values in HT were significantly lower than other plans (all p < 0.05), and those in TD were significantly lower than VMAT and ff-IMRT (all p < 0.05). However, there was no significant difference in the D2 and Dmean values between VMAT and ff-IMRT techniques (p > 0.05). No D98 and V100% parameters differed significantly among the 4 treatment types (p > 0.05). HT plans were provided for statistically significant improvement in HI (0.03 ± 0.01) compared to TD plans (0.05 ± 0.01, p = 0.003), VMAT (0.08 ± 0.03, p < 0.001), ff-IMRT (0.08 ± 0.01, p < 0.001). The HI revealed that TD was superior to VMAT and ff-IMRT (p < 0.05). The CI differed significantly for the 4 techniques of TD, HT, VMAT, and ff-IMRT (0.59 ± 0.10, 0.69 ± 0.11, 0.64 ± 0.09, and 0.64 ± 0.11, respectively; p = 0.035). The best CI was yielded by HT. We found no significant difference for the V5, V10, V15, V30, and the mean lung dose (MLD) among the 4 techniques (all p > 0.05). However, the V20 differed significantly among TD, HT, VMAT, and ff-IMRT (21.50 ± 7.20%, 19.50 ± 5.55%, 17.65 ± 5.45%, and 16.35 ± 5.70%, respectively; p = 0.047). Average V20 for the lungs was significantly improved by the TD plans compared to VMAT (p = 0.047), and ff-IMRT (p = 0.008). The V5 value of the lung in TD was 49.30 ± 13.01%, lower than other plans, but there was no significant difference (p > 0.05). The D1 of the spinal cord showed no significant difference among the 4 techniques (p = 0.056). CONCLUSIONS: All techniques are able to provide a homogeneous and highly conformal dose distribution. The TD technique is a good option for treating upper thoracic EC involvement. It could achieve optimal low dose to the lungs and spinal cord with acceptable PTV coverage. HT is a good option as it could achieve quality dose conformality and uniformity, while TD generated superior conformality.

Prognostic and predictive role of COX-2, XRCC1 and RASSF1 expression in patients with esophageal squamous cell carcinoma receiving radiotherapy.

Identification of biomarkers for predicting radiosensitivity would be useful for administering individualized radiotherapy (RT) to patients with esophageal cancer. The aim of the present study was to evaluate the association between cyclooxygenase-2 (COX-2), X-ray repair cross complementing group 1 (XRCC1), ras association domain family 1 (RASSF1) protein expression, clinicopathological characteristics, radiosensitivity and survival rate in 76 patients with esophageal squamous cell carcinoma (ESCC) who were treated with RT. Positive expression of COX-2, XRCC1 and RASSF1 was identified by immunohistochemistry in 81.6, 52.6 and 59.2% of ESCC cases, respectively. Negative COX-2 expression was associated with tumor (T) stage, node (N) stage, clinical stage and complete response (P<0.05), but not with gender, age, tumor location, differentiation degree, lesion length, progression-free survival (PFS) or overall survival (OS; P>0.05). XRCC1 expression was not associated with the clinicopathological features of ESCC, response to RT, PFS or OS. Positive RASSF1 expression was associated with the clinical stage, response to RT, PFS and OS (P<0.05), but not with gender, age, tumor location, T stage, N stage, differentiation degree or the lesion length (P>0.05). In the subgroup analysis, RASSF1 positive/XRCC1 negative expression was correlated with a longer median OS and PFS (P<0.05). Multivariate analyses revealed that the tumor response and RASSF1 expression were significant prognostic factors. Therefore, positive RASSF1 expression is associated with ESCC RT sensitivity, and may be a useful independent prognostic factor for ESCC.