Intelligent scoring system based on dynamic optical breast imaging for early detection of breast cancer.

Early detection of breast cancer can significantly improve patient outcomes and five-year survival in clinical screening. Dynamic optical breast imaging (DOBI) technology reflects the blood oxygen metabolism level of tumors based on the theory of tumor neovascularization, which offers a technical possibility for early detection of breast cancer. In this paper, we propose an intelligent scoring system integrating DOBI features assessment and a malignancy score grading reporting system for early detection of breast cancer. Specifically, we build six intelligent feature definition models to depict characteristics of regions of interest (ROIs) from location, space, time and context separately. Similar to the breast imaging-reporting and data system (BI-RADS), we conclude the malignancy score grading reporting system to score and evaluate ROIs as follows: Malignant (≥ 80 score), Likely Malignant (60-80 score), Intermediate (35-60 score), Likely Benign (10-35 score), and Benign (<10 score). This system eliminates the influence of subjective physician judgments on the assessment of the malignant probability of ROIs. Extensive experiments on 352 Chinese patients demonstrate the effectiveness of the proposed system compared to state-of-the-art methods.

Safer-by-design flame-sprayed silicon dioxide nanoparticles: the role of silanol content on ROS generation, surface activity and cytotoxicity.

BACKGROUND: Amorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles. RESULTS: Consistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content. CONCLUSION: Surface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.

Surface Immunoproteomics Reveals Potential Biomarkers in Alicyclobacillus acidoterrestris.

Alicyclobacillus acidoterrestris is a major putrefying bacterium that can cause pecuniary losses in the global juice industry. Current detection approaches are time-consuming and exhibit reduced specificity and sensitivity. In this study, an immunoproteomic approach was utilized to identify specific biomarkers from A. acidoterrestris for the development of new detection methods. Cell surface-associated proteins were extracted and separated by 2-D (two-dimensional) gel electrophoresis. Immunogenic proteins were detected by Western blot analysis using antisera against A. acidoterrestris. Twenty-two protein spots exhibiting immunogenicity were excised and eighteen of the associated spots were successfully identified by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS). These proteins were observed to be involved in energy and carbohydrate metabolism, transmembrane transport, response to oxidative stress, polypeptide biosynthesis, and molecule binding activity. This is the first report detailing the identification of cell surface-associated antigens of A. acidoterrestris. The identified immunogenic proteins could serve as potential targets for the development of novel detection methods.

Volume-staged Gamma Knife radiosurgery for orbital venous malformations.

OBJECTIVEThis article is a preliminary evaluation of the efficacy of volume-staged Gamma Knife radiosurgery (GKRS) in the treatment of patients with orbital venous malformations (OVMs).METHODSTwenty patients with moderate to large OVMs were treated with volume-staged GKRS between March 2005 and October 2015. The series included 8 male and 12 female patients with an average age of 22.5 years (range 9-45 years). The diagnoses were confirmed intraoperatively and at pathological examination in 14 cases and presumed in accordance with clinical and imaging findings in 6 cases. The median OVM volume was 12.2 cm3 (range 7.1-34.6 cm3). The median interval between stages was 10 months (range 6-12 months). The tumor margin dose for each stage ranged from 11.0 to 13.5 Gy. The median duration of follow-up was 45.5 months (range 18-98 months).RESULTSPeriodically scheduled MRI studies demonstrated evidence of a significant reduction of the original OVM volume in all cases. Visual acuity (VA) was preserved in 18 cases (90%). Five patients (25%) experienced vision improvement of varying degrees, and 13 (65%) experienced long-term preservation of VA at their pre-GKRS level. Deterioration in VA was observed in only 2 cases (10%). MRI demonstrated OVM regression after treatment in all cases, and all patients were found to have reduction of exophthalmos after volume-staged GKRS. Follow-up MRI revealed recurrence in only 1 case (5%). Three patients (15%) developed transient conjunctival edema.CONCLUSIONSThis retrospective investigation indicates that volume-staged GKRS provides an effective management option in selected patients with OVMs, providing excellent visual outcomes. The study adds substantial support for volume-staged GKRS as a major treatment for OVMs.

Assessment of reactive oxygen species generated by electronic cigarettes using acellular and cellular approaches.

Electronic cigarettes (e-cigs) have fast increased in popularity but the physico-chemical properties and toxicity of the generated emission remain unclear. Reactive oxygen species (ROS) are likely present in e-cig emission and can play an important role in e-cig toxicity. However, e-cig ROS generation is poorly documented. Here, we generated e-cig exposures using a recently developed versatile exposure platform and performed systematic ROS characterization on e-cig emissions using complementary acellular and cellular techniques: 1) a novel acellular Trolox-based mass spectrometry method for total ROS and hydrogen peroxide (H2O2) detection, 2) electron spin resonance (ESR) for hydroxyl radical detection in an acellular and cellular systems and 3) in vitro ROS detection in small airway epithelial cells (SAEC) using the dihydroethidium (DHE) assay. Findings confirm ROS generation in cellular and acellular systems and is highly dependent on the e-cig brand, flavor, puffing pattern and voltage. Trolox method detected a total of 1.2-8.9nmol H2O2eq./puff; H2O2 accounted for 12-68% of total ROS. SAEC cells exposed to e-cig emissions generated up to eight times more ROS compared to control. The dependency of e-cig emission profile on e-cig features and operational parameters should be taken into consideration in toxicological studies.

Fractionated Gamma Knife surgery for giant pituitary adenomas.

OBJECTIVE: To analyze the feasibility and effectiveness of fractionated Gamma Knife surgery (FGKS) for giant pituitary adenomas. METHODS: From June 2005 to May 2016, 14 patients with giant pituitary adenomas were treated with FGKS, and 10 patients (71%) completed follow-up evaluation. All patients had undergone surgical resection at least once prior to FGKS. The median-volume of the adenomas was 17.6cm3(range 4.9-61cm3). RESULTS: The median follow-up period was 31.5 months (range 6-58 months). The size of the tumors decreased in 6 patients and remained stable in 4 patients. The visual acuity improved in 1 patient. None of the patients suffered from vision deterioration caused by FGKS. CONCLUSION: FGKS is an effective treatment modality for giant pituitary adenomas in selected patients.

Gamma Knife surgery for brainstem metastases.

OBJECT: The goal of this study was to assess neuroimaging and clinical outcomes in patients harboring brainstem metastases that were treated with the Leksell Gamma Knife. METHODS: Twenty-eight patients with brainstem metastases (32 lesions: 8 midbrain, 21 pontine, and 3 medullary) were consecutively treated with GKS. The primary cancer diagnoses in this group included 22 cases of lung cancer, 5 cases of breast cancer, and 1 case of rectal cancer. The median age of the patients was 61 years (range 45-83 years). The median treated lesion volume was 0.78 cm(3) (range 0.03-5.6 cm(3)), and the median GKS margin dose was 16 Gy (range 12-20 Gy). Overall survival in these patients was calculated using the Kaplan-Meier method. RESULTS: The median survival time was 9 months after GKS (range 2-32 months). Survival was 39.3% at 1 year and 10.7% at 2 years. The tumor control rate in the series was 90.6% (29 of 32 lesions). Development of peritumoral edema occurred in 1 patient after GKS; 4 months after GKS, the edema disappeared. CONCLUSIONS: Gamma Knife surgery using a median margin dose of 16 Gy is a safe and effective local therapy for patients with brainstem metastases.

Same-day stereotactic aspiration and Gamma Knife surgery for cystic intracranial tumors.

OBJECT: The goal of this study was to evaluate the efficacy and safety of same-day stereotactic aspiration and Gamma knife surgery (GKS) for cystic intracranial tumors. METHODS: Between 1996 and 2007, 77 patients harboring cystic intracranial tumors underwent a same-day procedure of MRI-guided cyst aspiration followed by GKS. The diagnoses were metastatic tumor in 43 patients, glial tumor in 12 patients, vestibular schwannoma in 10 patients, craniopharyngioma in 9 patients, and hemangioblastoma in 3 patients. RESULTS: An improvement in symptoms was achieved in 68 patients (88.3%) immediately after cyst aspiration. The mean tumor volume in this group of patients was 25.1 cm(3) before aspiration and 11.1 cm(3) afterward. Hemorrhage during the course of aspiration was encountered in 1 patient. Transient nausea after cyst aspiration developed in 3 patients. There was no treatment-related hematoma, seizure, neurological deficit, or infection. The median follow-up period was 16 months (range 6-108 months). Tumor control was achieved in 50 (80.6%) of 62 patients who participated in follow-up for at least 6 months. CONCLUSIONS: The same-day stereotactic aspiration and GKS procedure was safe in patients with cystic brain tumors. Prompt symptom relief was obtained after cyst aspiration. The decrease in tumor volume following aspiration made GKS more effective because a higher prescription dose could be administered with a lower possibility of radiation-induced side effects.

Increased expression of EMMPRIN and VEGF in the rat brain after gamma irradiation.

The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.

Gamma knife radiosurgery for primary orbital varices: a preliminary report.

AIM: The aim of this retrospective study is to evaluate the authors' experience using gamma knife radiosurgery in the management of primary orbital varices. METHODS: Fourteen patients, six males and eight females, with ages ranging from 7 to 56 years of age, were treated with gamma knife radiosurgery from April 2001 to June 2005 for primary orbital varices. The median prescription peripheral dose was 16 Gy, ranging from 15 to 20 Gy, and the median maximum dose was 32 Gy, ranging from 30 to 40 Gy. The median volume of the lesion at radiosurgery was 4.5 ml (range 1.9 ml to 9.0 ml). The mean dose to optic nerve was below 10 Gy. A mean of 10 isocentres (range 8 to 13) were used for treating these lesions. RESULTS: At a median follow-up period of 36 months (range 18 to 66 months), recurrent exophthalmos and diplopia resolved in 10 patients. Two of the remaining four patients showed evidence of decrease in distensibility, while the other two remain unchanged. The median time of their presenting symptoms resolving was 7 months (range 3 to 18 months). One patient lost her sight 18 months after gamma knife radiosurgery. No patient had intraorbital haemorrhage after treatment. CONCLUSION: Gamma knife radiosurgery provides effective long-term relief of symptoms in selected patients with primary orbital varices.

Long-term results of Gamma Knife surgery for optic nerve sheath meningioma.

OBJECT: The goal of this study was to assess the long-term results of Gamma Knife surgery (GKS) in patients harboring an optic nerve sheath meningioma (ONSM). METHODS: Thirty patients harboring an ONSM were treated with GKS between 1998 and 2003. Gamma Knife surgery was performed as the sole treatment option in 21 of these patients and resection had been performed previously in 9 patients. The mean volume of the tumor at the time of GKS was 3.6 cm(3) (range 1.4-9.7 cm(3)), and the mean prescription peripheral dose was 13.3 Gy (range 10-17 Gy). The mean number of isocenters used to treat these lesions was 8 (range 5-14 isocenters). RESULTS: At a median follow-up of 56 months, visual acuity improved in 11 patients, remained stable in 13 patients (including 4 patients who were completely blind before GKS), and deteriorated in 6 patients. Follow-up images were available in all patients and showed tumor regression in 20 patients and stable tumor in 8 patients. Persistent imaging evidence of progression was only present in 2 patients. With the exception of reversible conjunctival edema in 4 cases, no other serious acute side effect was observed. CONCLUSIONS: Gamma Knife surgery provides long-term tumor control for ONSM. The results of this study add substantial evidence that GKS may definitely become a standard treatment approach in selected cases of ONSM.

Gamma Knife surgery in the management of orbital tumors.

OBJECT: The authors evaluated the results they obtained using Gamma Knife surgery (GKS) in patients with orbital tumors. METHODS: This is a retrospective clinical evaluation of 202 patients with orbital tumors who were treated with GKS between September 1995 and October 2008. The series included 84 men and 118 women with a mean age of 39.5 ± 14.6 years (range 5-85 years). The diagnoses were determined based on pathological analyses in 113 patients and presumed based on characteristic clinical and imaging findings in 89 patients. There were 84 meningiomas, 38 epithelial tumors of the lacrimal gland, 23 schwannomas, 18 malignant choroidal melanomas, 12 optic nerve gliomas, 11 orbital metastases, 10 pseudotumors of the orbit, 3 retinoblastomas, and 3 cases of fibromatosis. The median target volume was 5.4 cm(3) (range 0.04-35.6 cm(3)). The tumor margin dose ranged from 10 to 40 Gy. RESULTS: At a median follow-up period of 34.5 ± 14.7 months (range 12-114 months), tumor shrinkage was observed in 118 patients (58.4%) and stable tumor size in 71 patients (35.1%). Regularly scheduled neuroimaging studies demonstrated evidence of tumor progression in only 13 patients (6.4%): 9 of these patients underwent repeated GKS and 4 received surgical treatment. Visual acuity was preserved in 129 patients. Seventy-two patients experienced some degree of improvement in vision. Severe deterioration of visual acuity was found in 18 of 147 patients who had useful vision before treatment. Nineteen patients (9.4%) experienced transient conjunctival edema; no other serious acute side effect was observed. CONCLUSIONS: Gamma Knife surgery provides an effective management strategy in patients with orbital tumors; it achieves excellent preservation of neurological function and is associated with few treatment-related complications.

Radiosensitivity of glioma to Gamma Knife treatment enhanced in vitro and in vivo by RNA interfering Ku70 that is mediated by a recombinant adenovirus.

OBJECT: The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT). METHODS: First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3'(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase-9 were determined using immunohistochemical analyses. RESULTS: The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged. CONCLUSIONS: Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy-mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.

Combination therapy with Gamma Knife radiosurgery and antisense EGFR for malignant glioma in vitro and orthotopic xenografts.

Accumulating evidence has indicated that epidermal growth factor receptor (EGFR) signaling pathway plays a potentially important role in mediating radiation resistance in human gliomas. In this study, we aimed to evaluate the effect of combination therapy with Gamma Knife radiosurgery (GKR) and antisense EGFR for malignant glioma in vitro and orthotopic xenografts. GKR and down-regulation of EGFR expression by antisense EGFR resulted in significant suppression of cell proliferation and induction of cell apoptosis in vitro. Moreover, the growth of the C6 glioma in orthotopic xenografts was significantly inhibited by this combination treatment. Thus, our results indicate that down-regulation of EGFR expression enhanced the radiosensitivity of glioma and GKR in combination with antisense EGFR is a potential strategy for glioma therapy.

Gamma Knife surgery in patients harboring orbital cavernous hemangiomas that were diagnosed on the basis of imaging findings.

OBJECT: This study was undertaken to evaluate clinical outcomes and tumor control in patients harboring orbital cavernous hemangiomas (OCHs) that had been diagnosed based on findings of imaging studies and treated by Gamma Knife surgery (GKS). METHODS: Between 1995 and 2008, 23 patients harboring OCHs that had been diagnosed on the basis of imaging findings were treated using GKS; complete follow-up data are available in all cases. The median treatment volume was 1.5 cm³ (range 0.15-10.10 cm³), the median tumor margin dose was 15 Gy (range 12-20 Gy), and the median follow-up period was 12 months (range 6-120 months). RESULTS: A decrease in tumor size was found in 20 patients, and no tumor progression was observed after GKS. Eleven of 14 patients whose visual function had been adversely affected prior to treatment had improved visual acuity at the last assessment. Side effects of the procedure included orbital pain in 3 patients and chemosis in 2 patients. CONCLUSIONS: In this preliminary experience, GKS proved to be an effective treatment for OCHs diagnosed on the basis of imaging findings. Additional follow-up is necessary, and the long-term side effects of the procedure still need to be determined.

Long-term outcomes after Gamma Knife surgery for vestibular schwannomas: a 10-year experience.

OBJECT: The authors sought to assess the results of Gamma Knife surgery (GKS) in patients with vestibular schwannomas (VSs). METHODS: Seventy-four consecutive patients (33 men and 41 women) were evaluated by means of serial imaging studies, clinical examinations, and questionnaires. Nineteen patients had undergone resection of their VS. Facial nerve function was normal in 63 patients (85.1%) before GKS, and 63.5% of them had useful hearing. The prescription peripheral dose varied between 10 and 14 Gy (mean 12.27 +/- 0.96 Gy); the corresponding central dose was 21 to 30 Gy (mean 24.9 +/- 2.18 Gy). The mean volume of the tumor at GKS was 10.79 +/- 5.52 ml (range 0.11-27.8 ml). A mean of eight isocenters (range 3-17) was used for treating these lesions. At a median follow-up period of 68.3 months (range 30-122 months), tumor shrinkage was observed in 60 patients (81.1%), and the tumor size was stable in 11 (14.8%). Persistent neuroimaging demonstrated evidence of progression in only three patients (4.1%): two underwent repeated GKS after an interval of 18 months and one continues to be observed. Five patients experienced trigeminal dysfunction: in three the dysfunction was transient and in the other two the dysfunction persists. Three patients suffered facial palsy. Useful hearing was preserved in 34 patients. Thirteen patients experienced some degree of hearing improvement. Deterioration of hearing was found in 13 of 62 patients who had Class I or II hearing before treatment. CONCLUSIONS: Gamma Knife surgery prevents tumor growth; it achieves excellent neurological function preservation and produces few treatment-related complications.