Yuliang Jiang

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.

Percutaneous computed tomography/ultrasonography-guided permanent iodine-125 implantation as salvage therapy for recurrent squamous cell cancers of head and neck

Objective: To assess the feasibility, efficacy, and morbidity of permanent percutaneous 125I seed implantation under computed tomography (CT)/ultrasonography guidance for recurrent squamous cell carcinomas of head and neck. Methods: Twenty-five patients underwent 125I seed implantation under CT or ultrasonography guidance. Postoperative dosimetry was routinely performed for all the patients. The actuarial D90 of the implanted 125I seeds ranged from 90 Gy to 160 Gy (median: 130 Gy). The activity of 125I seed ranged from 0.35 mCi to 0.8 mCi (median: 0.6 mCi). The total number of seeds implanted ranged from 3 to 61 (median: 22). The follow-up period ranged from 3 to 40 months (median: 8 months). Results: The median local disease-free progression was 12 months (95% CI, 4.8–19.2), and the 1- and 2-year local tumor control rates were 48.7% and 39.9%, respectively. The 1- and 2-year survival rates were 42.5% and 28.3%, respectively (median: 11 months) (95% CI, 8.2–13.8). Of the 25 patients, 6 (24%) died of local recurrence and 5 (20%) died of metastases; 2 patients showed recurrences at 3 and 8 months after seed implantation and subsequently died of pneumonia. One patient died of heart disease. One developed ulceration with tumor progression. Blood vessel damage and neuropathy were not observed. Conclusion: The high local tumor control rates, minimal invasion, and low morbidity suggest that percutaneous 125I seed implantation is a feasible and safe salvage for patients with recurrent squamous cell carcinomas of the head and neck.

An investigation of 125I seed permanent implantation for recurrent carcinoma in the head and neck after surgery and external beam radiotherapy

BackgroundA preliminary assessment was conducted of the feasibility, efficacy, and morbidity of 125I seed implantation for recurrent head and neck carcinoma after surgery and external beam radiotherapy.MethodsNineteen patients with recurrent head and neck carcinomas underwent 125I seed implantation under ultrasound or computed tomography guidance. The actuarial D90 of 125I seed implantation ranged from 90 to 160 Gy (median, 131 Gy). The follow-up period ranged from 3 to 44 months (median, 11 months).ResultsThe median local control was 24 months (95% confidence interval, 10.2 to 37.8). The one- year, two-year and three-year local controls were 73.3%, 27.5% and 27.5%, respectively, whereas the one-year, two-year and three-year survival rates were 53.0%, 18.2% and 18.2%, respectively, and the median survival was 13 months (95% confidence interval, 6.6 to 19.4). A total of 26.3% of patients (5/19) died of local recurrence and 21.1% of patients (4/19) died of metastases. One suffered from a grade 1 skin reaction.Conclusions125I seed implantation is feasible and safe as a salvage treatment for patients with recurrent head and neck cancers. The high local control results and low morbidity merits further investigation.

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.

Genotype/phenotype analysis in Chinese laminin‐α2 deficient congenital muscular dystrophy patients

Laminin‐α2 deficient congenital muscular dystrophy (CMD) is an autosomal recessive disorder characterized by severe muscular dystrophy, which is typically associated with abnormal white matter. In this study, we assessed 43 CMD patients with typical white matter abnormality and laminin‐α2 deficiency (complete or partial) diagnosed by immunohistochemistry to determine the clinical and molecular genetic characteristics of laminin‐α2 deficient CMD. LAMA2 gene mutation analysis was performed by direct sequencing of genomic DNAs. Exonic deletion or duplication was identified by multiplex ligation‐dependent probe amplification (MLPA) and verified by high‐density oligonucleotide‐based CGH microarrays. Gene mutation analysis revealed 86 LAMA2 mutations (100%); 15 known and 37 novel. Among these mutations, 73.9% were nonsense, splice‐site or frameshift and 18.8% were deletions of one or more exons. Genetic characterization of affected families will be valuable in prenatal diagnosis of CMD in the Chinese population.

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.

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.

Image-Guided Percutaneous 125I Seed Implantation as a Salvage Treatment for Recurrent Soft Tissue Sarcomas After Surgery and Radiotherapy

The purpose of this study was to evaluate the safety and efficacy of percutaneous iodine-125 ((125)I) seed implantation using computed tomography (CT) or ultrasound guidance in the treatment of recurrent soft tissue malignancies after surgery and radiotherapy. From February 2002 to September 2009, 18 patients with recurrent soft tissue sarcomas were treated under ultrasound or CT guidance. The actuarial median number of (125)I seeds implanted was 35 (range, 6-129), and the actuarial D90 of the implanted (125)I seeds ranged from 107.9 to 204.4 Gy (median, 147.1 Gy). The activity of the seeds ranged from 0.4 to 0.8 mCi (median, 0.7 mCi). Follow-up times ranged from 4 to 78 months (median, 20 months). The median local control was 41 months (95% CI, 15.9-66.1 months). The 1-, 2-, 3-, 4-, and 5-year local controls were 78.8%, 78.8%, 78.8%, 26.3%, and 0%, respectively. The median survival was 32 months (95% CI, 16-48 months). The actuarial 1-, 2-, 3-, 4-, and 5-year survivals were 76.6%, 61.3%, 39.4%, 39.4%, and 39.4%, respectively. Seven (7) patients (38.9%) experienced recurrence after seed implantation. Six (6) patients (33.3%) died of distant metastases and 1 died of stroke. Two (2) patients developed ulceration, 1 case caused by recurrence and another by a reaction of the skin to radiation. Percutaneous (125)I seed implantation for recurrent soft tissue malignancies under CT or ultrasound guidance is safe and is associated with high efficacy and low morbidity.