Suqing Tian

Intraoperative ultrasound-guided iodine-125 seed implantation for unresectable pancreatic carcinoma.

BackgroundTo assess the feasibility and efficacy of using 125I seed implantation under intraoperative ultrasound guidance for unresectable pancreatic carcinoma.MethodsFourteen patients with pancreatic carcinoma that underwent laparotomy and considered unresectable were included in this study. Nine patients were pathologically diagnosed with Stage II disease, five patients with Stage III disease. Fourteen patients were treated with 125I seed implantation guided by intraoperative ultrasound and received D90 of 125I seeds ranging from 60 to 140 Gy with a median of 120 Gy. Five patients received an additional 35–50 Gy from external beam radiotherapy after seed implantation and six patients received 2–6 cycles of chemotherapy.Results87.5% (7/8) of patients received partial to complete pain relief. The response rate of tumor was 78.6%, One-, two-and three-year survival rates were 33.9% and 16.9%, 7.8%, with local control of disease achieved in 78.6% (11/14), and the median survival was 10 months (95% CI: 7.7–12.3).ConclusionThere were no deaths related to 125I seed implant. In this preliminary investigation, 125I seed implant provided excellent palliation of pain relief, local control and prolong the survival of patients with stage II and III disease to some extent.

SDF-1/CXCR4 Axis Regulates Cell Cycle Progression and Epithelial-Mesenchymal Transition via Up-regulation of Survivin in Glioblastoma.

Stromal cell-derived factor 1 (SDF-1)/CXCR4 ligand-receptor axis is widely recommended as an attractive target for cancer therapy. Meanwhile, epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. As one of inhibitors of apoptosis proteins, survivin is implicated in the onset and development of cancer. In the present study, we tried to determine the cause-effect associations between SDF-1/CXCR4 axis and survivin expression in glioblastoma U-251 cell line. Survivin activation and inhibition were induced with exogenous SDF-1 and survivin small interfering RNA (survivin siRNA), respectively. Western blot was used to detect relevant proteins in SDF-1/CXCR4 axis. Western blot analysis revealed that survivin expression in U-251 increased in a dose- and time-dependent manner in response to SDF-1 treatment. However, the interference with MEK/ERK and PI3K/AKT pathway prohibited SDF-1-induced survivin up-regulation. Importantly, survivin knockdown abrogated cell cycle progression and the expression of snail and N-cadherin, compared with non-transfectants. In conclusion, the present study shows that SDF-1 up-regulates survivin via MEK/ERK and PI3K/AKT pathway, leading to cell cycle progression and EMT occurrence dependent on survivin. The blockade of survivin will allow for the treatment of glioblastoma.

RETRACTED ARTICLE: Bone morphogenetic protein 2 mediates epithelial-mesenchymal transition via AKT and ERK signaling pathways in gastric cancer

Although deregulation of bone morphogenetic protein 2 (BMP2) signaling has been linked to various types of cancers, the relationships between abnormal activation of these signaling pathways and tumorigenesis are not clear in gastric cancer. We hypothesized that BMP2 might be involved in epithelial-mesenchymal transition (EMT) process of gastric cancer. Here, BMPR-II activation and inhibition in gastric cancer cell line AGS were induced with exogenous BMP2 and with BMPR-II small interfering RNA (siRNA), respectively. BMPR-II downstream signal molecules AKT, ERK phosphorylation, and EMT biomarkers (vimentin, snail, N-cadherin, and E-cadherin) were tested using the Western blot. In the present study, our results showed that BMP2 can induce AKT and ERK phosphorylation in a dose-dependent method, and endogenous BMPR-II can be inhibited completely by BMPR-II siRNA in AGS. Notably BMP2 alone treatment can induce the up-regulation of vimentin, snail, and N-cadherin in AGS cells, besides, the down-regulation of E-cadherin also occurred. On the contrary, BMPR-II siRNA significantly prohibited BMP2-induced AKT and ERK phosphorylation, at the same time, EMT biomarkers changes were not observed. On the other hand, BMPR-II knockdown could significantly affect AGS wound closure and the migration ability (p < 0.001) compared to control siRNA and BMP2 alone. In conclusion, this study suggested that EMT process can be triggered by the BMP2/BMPR axis in gastric cancer and then involved in the tumor cell migration, invasion, and metastasis via the activation of PI3K/AKT and MEK/ERK pathways. Our study lays a new foundation for the treatment of gastric cancer through antagonizing BMP2 system.

Retraction Note to “SDF-1/CXCR4 Axis Regulates Cell Cycle Progression and Epithelial-Mesenchymal Transition via Up-regulation of Survivin in Glioblastoma”

Stromal cell-derived factor 1 (SDF-1)/CXCR4 ligand-receptor axis is widely recommended as an attractive target for cancer therapy. Meanwhile, epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. As one of inhibitors of apoptosis proteins, survivin is implicated in the onset and development of cancer. In the present study, we tried to determine the cause-effect associations between SDF-1/CXCR4 axis and survivin expression in glioblastoma U-251 cell line. Survivin activation and inhibition were induced with exogenous SDF-1 and survivin small interfering RNA (survivin siRNA), respectively. Western blot was used to detect relevant proteins in SDF-1/CXCR4 axis. Western blot analysis revealed that survivin expression in U-251 increased in a dose- and time-dependent manner in response to SDF-1 treatment. However, the interference with MEK/ERK and PI3K/AKT pathway prohibited SDF-1-induced survivin up-regulation. Importantly, survivin knockdown abrogated cell cycle progression and the expression of snail and N-cadherin, compared with non-transfectants. In conclusion, the present study shows that SDF-1 up-regulates survivin via MEK/ERK and PI3K/AKT pathway, leading to cell cycle progression and EMT occurrence dependent on survivin. The blockade of survivin will allow for the treatment of glioblastoma.

Interstitial 125I Seed Implantation for Cervical Lymph Node Recurrence after Multimodal Treatment of Thoracic Esophageal Squamous Cell Carcinoma

This study aimed to analysis outcome and prognosis of interstitial 125I seed implantation in patients with cervical lymph node recurrence after multimodal treatment of thoracic esophageal squamous cell carcinoma (ESCC). We conducted a retrospective review of 19 patients with 32 cervical lymph nodes recurrences after multimodal treatment (lymphadenectomy, radiotherapy, chemotherapy, and various combinations of these treatments) of thoracic ESCC, who underwent 125I seed implantation in our department from 2003 to 2011. All the patients were followed up until expiration and the median duration of follow up was 7 months (range, 3-44 months). Syndromes significantly improved after implantation. The local control rates after 3, 6, 12, and 24 months were 84.2%, 63.2%, 32.0%, and 26.0%, respectively, with a median of 10 months. The median overall survival time was 7 months (95% CI, 5.6-8.4), and 1- and 2-year survival rates were 31.6% and 10.5%, respectively. Among these patients, there were 11 died of progression of disease (PD) 3-44 months after implantation. One patient presented grade IV skin toxic effect and repaired by free flap transplantation. No fatal complications such as massive bleeding happened. In univariate analysis, N stage, number of recurrent nodes, recurrence interval time, and D90 were prognostic factors of the tumor local control and survival (p = 0.131 vs. 0.029, 0.129 vs. 0.071, 0.042 vs. 0.042, and 0.056 vs. 0.065, respectively). Multivariate analysis demonstrated that N stage, number of recurrent nodes, and recurrence interval time were independent prognostic factors of the tumor local control (p = 0.022, 0.019, and <0.001, respectively), and recurrence interval time was prognostic factor of the survival (p < 0.001). Interstitial 125I seed implantation is a safe and effective salvage treatment for cervical lymph node recurrence after multimodal treatment. The N stage, number of recurrent nodes and recurrence interval time are factors influencing tumor local control, and the recurrence interval time is independent factor influencing survival after percutaneous 125I seed implantation in ESCC with cervical lymph node recurrence.

Management of recurrent alveolar soft-part sarcoma of the tongue after external beam radiotherapy with iodine-125 seed brachytherapy.

Alveolar soft part sarcoma (ASPS) is a rare type of soft tissue sarcoma. The infrequency of ASPS is such that it accounts for <1% of all soft tissue sarcomas and <0.1% of sarcomas concerning the head and neck, primarily those involving the orbit (48%) and tongue (25%). Traditional chemotherapy or radiotherapy of ASPS is often associated with poor outcome, even after comprehensive interventions.

CT-Guided 125I Seed Interstitial Brachytherapy as a Salvage Treatment for Recurrent Spinal Metastases after External Beam Radiotherapy

The aim of this study is to evaluate the feasibility, safety, and clinical efficacy of CT-guided 125I seed interstitial brachytherapy in patients with recurrent spinal metastases after external beam radiotherapy (EBRT). Between August 2003 and September 2015, 26 spinal metastatic lesions (24 patients) were reirradiated by this salvage therapy modality. Treatment for all patients was preplanned using a three-dimensional treatment planning system 3–5 days before 125I seed interstitial brachytherapy; dosimetry verification was performed immediately after seed implantation. Median actual D 90 was 99 Gy (range, 90–176), and spinal cord median D max was 39 Gy (range, 6–110). Median local control (LC) was 12 months (95% CI: 7.0–17.0). The 6- and 12-month LC rates were 52% and 40%, respectively. Median overall survival (OS) was 11 months (95% CI: 7.7–14.3); 6-month and 1-, 2-, and 3-year OS rates were 65%, 37%, 14%, and 9%, respectively. Pain-free survival ranged from 2 to 42 months (median, 6; 95% CI: 4.6–7.4). Treatment was well-tolerated, with no radiation-induced vertebral compression fractures or myelopathy reported. Reirradiation with CT-guided 125I seed interstitial brachytherapy appears to be feasible, safe, and effective as pain relief or salvage treatment for patients with recurrent spinal metastases after EBRT.

Computed Tomography (CT)-guided Interstitial Permanent Implantation of 125I Seeds for Refractory Chest Wall Metastasis or Recurrence

To evaluate the efficacy and safety of 125I seeds implantation for refractory chest wall (CW) metastasis or recurrence under CT guidance. In addition we assessed initial data obtained on the therapeutic response for refractory CW metastasis or recurrence. Twenty consecutive patients underwent permanent implantation of 125I seeds (from Jul. 2004 to Jan. 2011) under computed tomography (CT) guidance. Postoperative dosimetry was routinely performed for all patients. The actuarial D90 of the implanted 125I seeds ranged from 100 Gy to 160 Gy (median: 130 Gy). The activity of 125I seeds ranged from 0.5 mCi to 0.78 mCi (median: 0.71 mCi). The total number of seeds implanted ranged from 8 to 269 (median: 53). The follow-up period ranged from 3 to 54 months (median: 11.5 months). The survival and local control probabilities were calculated by the Kaplan-Meier method. Among all the 20 patients, 3 patients had complete remission CR (15%), 12 patients had partial remission PR (60%), 5 patients had stable disease SD. The 1-, 2-, 3- and 4-year tumor control rates were all 88.7% respectively. The 1- and 2-, 3-, 4-year cancer specific survival rates were 56.5% and 47.1%, 47.1%, 47.1% respectively. The 1- and 2-, 3-, 4-year overall survival rates were 53.3% and 35.6%, 35.6%, 35.6% respectively, with a median survival of 15 months (95% CI, 7.0-22.9). Mild brachial plexus injury was seen in one patient; grade 1 or 2 skin reactions were seen in 6 patients (30%) who had received external beam radiation therapy (EBRT) before. No grade 3 and 4 skin side effects were found. Rib fracture, ulceration, pneumothorax or hemopneumothorax were not seen. Interstitial permanent implantation of 125I seeds under CT guidance is feasible, efficacious and safe for refractory CW metastasis or recurrence.

A Hybrid IMRT/VMAT Technique for the Treatment of Nasopharyngeal Cancer

Hybrid IMRT/VMAT technique which combined intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) was developed for the treatment of nasopharyngeal cancer (NPC). Two-full-arc VMAT (2ARC-VMAT), 9-field IMRT (9F-IMRT), and Hybrid IMRT/VMAT plans for NPC were compared in terms of the dosimetric quality, sparing of organs at risk (OARs), and delivery efficiency. The Hybrid IMRT/VMAT technique can improve the target dose homogeneity and conformity compared with 9F-IMRT and 2ARC-VMAT. It can reduce the dose delivered to the TMJ, mandible, temporal lobe, and unspecified tissue with fewer MUs compared with 9F-IMRT and dose delivered to parotids, brainstem, and spinal cord compared with 2ARC-VMAT technique. The mean delivery time of Hybrid plans was shorter than that of 9F-IMRT plans (408 s versus 812 s; P = 0.00) and longer than that of 2ARC-VMAT plans (408 s versus 179 s; P = 0.00). Hybrid IMRT/VMAT technique could be a viable radiotherapy technique with better plan quality.