Purpose: Various studies have investigated 3-dimensional (3D)-printed implants using Ti6Al-4V powder; however, multi-root 3D-printed implants have not been fully investigated. The purpose of this study was to explore the stability of multirooted 3D-printed implants with lattice and solid structures. The secondary outcomes were comparisons between the 2 types of 3D-printed implants in micro-computed tomographic and histological analyses. Methods: Lattice- and solid-type 3D-printed implants for the left and right mandibular third premolars in beagle dogs were fabricated. Four implants in each group were placed immediately following tooth extraction. Implant stability measurement and periapical X-rays were performed every 2 weeks for 12 weeks. Peri-implant bone volume/tissue volume (BV/TV) and bone mineral density (BMD) were measured by micro-computed tomography. Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were measured in histomorphometric analyses. Results: All 4 lattice-type 3D-printed implants survived. Three solid-type 3D-printed implants were removed before the planned sacrifice date due to implant mobility. A slight, gradual increase in implant stability values from implant surgery to 4 weeks after surgery was observed in the lattice-type 3D-printed implants. The marginal bone change of the surviving solid-type 3D-printed implant was approximately 5 mm, whereas the value was approximately 2 mm in the lattice-type 3D-printed implants. BV/TV and BMD in the lattice type 3D-printed implants were similar to those in the surviving solid-type implant. However, BIC and BAFO were lower in the surviving solid-type 3D-printed implant than in the lattice-type 3D-printed implants. Conclusions: Within the limits of this preclinical study, 3D-printed implants of double-rooted teeth showed high primary stability. However, 3D-printed implants with interlocking structures such as lattices might provide high secondary stability and successful osseointegration.
Kim, Il-Han;Choi, Eun-Kyung;Ha, Sung-Whan;Park, Charn-Il;Cha, Chang-Yong
Radiation Oncology Journal
/
v.6
no.1
/
pp.1-11
/
1988
Recovery from potentially lethal damage (PLDR) after irradiation was studied in plateau-phase culture of Vero cells in vitro. Unfed plateau-phase cells were irradiated with dose of 1 to 9Gy using Cs-137 irradiator. Cells then were incubated again and left in situ for 0, 1, 2, 3, 4, 5, 6, and 24 hours and then were trypsinized explanted, and subcultured in fresh RPMI-1640 media containing $0.33\%$ agar. Cell survival was measured by colony forming ability. An adequate number of heavily irradiated Vero cells were added as feeder cells to make the total cell number constant in every culture dish. As the postirradiation in situ incubation time increased, surviving fraction increased by PLDR. The rate of PLDR was so rapid that increased surviving fraction reached saturation level at 2 to 4 hours after in situ incubation. As the radiation dose increased, the rate of PLDR fastened and the magnitude of increased surviving fraction at saturation level by PLOR also increased. In analysis of cell survival curve fitted to the linear-quadratic model, the linear inactivation coefficient $(\alpha)$ decreased largely and reached nearly to zero but the quadratic inactivation coefficient $(\beta)$ increased minimally by increment of postirradiation in situ incubation time. So PLDR mainly affected the damage expressed as $\alpha$, In the multitarget model, significant change was not obtained in $D_0\;but\;in D_q$. Therefore, shoulder region in cell survival curve was mainly affected by PLDR and terminal slope was not influenced at all. And dose-modifying factor by PLDR was relatively higher in shoulder region, that is, in low dose area below 3 Gy.
Purpose: The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors. Materials and Methods: We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients. Results: The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. ${\leq}90$ Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed. Conclusion: Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.
Ligusticum chuanxiong (Umbelliferae) is a perennial herb that has been used for invigoration of blood in Korean traditional medicine. It is especially important in gynecological therapy of amenorrhea and dysmenorrhea. In this study, the essential oil of L. chuanxiong was obtained by steam distillation and its main components of L. chuanxiong, Z-ligustilide and butylidene phthalide, were isolated by silica gel column chromatography. We investigated the cytotoxic effects of the essential oil fraction of L. chuanxiong and its main components on MCF-7, HeLa and SK-Hep-1 cell lines by measuring the number of surviving cancer cells after treatment through direct cell counting and MTT analysis, and by examining the morphological changes under the microscope. The essential oil from the rhizomes of L. chuanxiong and its main components showed significant cytotoxic activities for all three tested cell lines. We also observed morphological changes of shrinking and blebbing in the membranes of the three cell lines, depending on the concentration of L. chaunxiong oil or its main components.
Background: In this study, various types of deep-learning models for predicting in vitro radiosensitivity from gene-expression profiling were compared. Methods: The clonogenic surviving fractions at 2 Gy from previous publications and microarray gene-expression data from the National Cancer Institute-60 cell lines were used to measure the radiosensitivity. Seven different prediction models including three distinct multi-layered perceptrons (MLP), four different convolutional neural networks (CNN) were compared. Folded cross-validation was applied to train and evaluate model performance. The criteria for correct prediction were absolute error < 0.02 or relative error < 10%. The models were compared in terms of prediction accuracy, training time per epoch, training fluctuations, and required calculation resources. Results: The strength of MLP-based models was their fast initial convergence and short training time per epoch. They represented significantly different prediction accuracy depending on the model configuration. The CNN-based models showed relatively high prediction accuracy, low training fluctuations, and a relatively small increase in the memory requirement as the model deepens. Conclusion: Our findings suggest that a CNN-based model with moderate depth would be appropriate when the prediction accuracy is important, and a shallow MLP-based model can be recommended when either the training resources or time are limited.
Background: We investigated the feasibility of in vitro radiosensitivity prediction with gene expression using deep learning. Methods: A microarray gene expression of the National Cancer Institute-60 (NCI-60) panel was acquired from the Gene Expression Omnibus. The clonogenic surviving fractions at an absorbed dose of 2 Gy (SF2) from previous publications were used to measure in vitro radiosensitivity. The radiosensitivity prediction model was based on the convolutional neural network. The 6-fold cross-validation (CV) was applied to train and validate the model. Then, the leave-one-out cross-validation (LOOCV) was applied by using the large-errored samples as a validation set, to determine whether the error was from the high bias of the folded CV. The criteria for correct prediction were defined as an absolute error<0.01 or a relative error<10%. Results: Of the 174 triplicated samples of NCI-60, 171 samples were correctly predicted with the folded CV. Through an additional LOOCV, one more sample was correctly predicted, representing a prediction accuracy of 98.85% (172 out of 174 samples). The average relative error and absolute errors of 172 correctly predicted samples were 1.351±1.875% and 0.00596±0.00638, respectively. Conclusion: We demonstrated the feasibility of a deep learning-based in vitro radiosensitivity prediction using gene expression.
Hai Huang;Xiaoting Yuan;Longjingrui Ma;Jiwei Lin;Guopeng Zhang;Bin Cai
Nuclear Engineering and Technology
/
v.55
no.6
/
pp.2298-2304
/
2023
Titanium alloys are expected to become one of the candidate materials for nuclear-powered spacecraft due to their excellent overall performance. Nevertheless, atomistic mechanisms of the defect accumulation and evolution of the materials due to long-term exposure to irradiation remain scarcely understood by far. Here we investigate the heavy irradiation damage in a-titanium with a dose as high as 4.0 canonical displacements per atom (cDPA) using atomistic simulations of Frenkel pair accumulation. Results show that the content of surviving defects increases sharply before 0.04 cDPA and then decreases slowly to stabilize, exhibiting a strong correlation with the system energy. Under the current simulation conditions, the defect clustering fraction may be not directly dependent on the irradiation dose. Compared to vacancies, interstitials are more likely to form clusters, which may further cause the formation of 1/3<1210> interstitial-type dislocation loops extended along the (1010) plane. This study provides an important insight into the understanding of the irradiation damage behaviors for titanium.
Experiments have been carried out with C3H mouse fibrosarcoma (FSa II) to determine the effect of different sequence and time intervals between irradiation and administration of cis-diammihedichloroplatinum (cis-DDP) with gross tumors (6 mm in diameter), microscopic tumors (3 days after transplantation of $10^3$ cells) and cells in culture. The drug was administered either 24, 12, 8, 4, 2, 1, 0.5 hour before irradiation, immediately before irradiation, or 0.5, 1, 2, 4, 8, 12, 24 hours after irradiation. In case of in vivo studies, tumor growth delay was used as an end point. Clonogenic cell surviving fraction was used for in vitro studies. Tumor growth delay for gross tumor after 10 Gy radiation plus 10 mg/kg cis-DDP ranged from 6.3 to 10.66 days and the enhancement ratio ranged from 1.37 to 2.23. The most effective combination was when cis-DDP was given 4 hours before irradiation. Tumor growth delay for microscopic tumor after 5 Gy of radiation and 5 mg/kg of cis-DDP ranged from 3.55 to 11.98 days with enhancement ratio from 2.05 to 6.92. Microscopic tumors showed response significantly greater than additive in every time interval and the most effective treatments were when cis-DDP was given 2 and 1 hour before irradiation. In in vitro experiment, the surviving fraction after 6 Gy of radiation and 1 hour exposure to 4 ${\mu}M$ cis-DDP fluctuated as a function of time between treatments, but the difference between maximum and minimum surviving fractions was very small. According to the above results the sequence and time interval between irradiation and chemotherapy is very critical especially for the management of microscopic tumors as in the case of postoperative adjuvant treatment.
$\underline{Purpose}$: To evaluate biological characteristics of neutron beam generated by MC50 cyclotron located in the Korea Institute of Radiological and Medical Sciences (KIRAMS). $\underline{Materials\;and\;Methods}$: The neutron beams generated with 15 mm Beryllium target hit by 35 MeV proton beam was used and dosimetry data was measured before in-vitro study. We irradiated 0, 1, 2, 3, 4 and 5 Gy of neutron beam to EMT-6 cell line and surviving fraction (SF) was measured. The SF curve was also examined at the same dose when applying lead shielding to avoid gamma ray component. In the X-ray experiment, SF curve was obtained after irradiation of 0, 2, 5, 10, and 15 Gy. $\underline{Results}$: The neutron beams have 84% of neutron and 16% of gamma component at the depth of 2 cm with the field size of $26{\times}26\;cm^2$, beam current $20\;{\mu}A$, and dose rate of 9.25 cGy/min. The SF curve from X-ray, when fitted to linear-quadratic (LQ) model, had 0.611 as ${\alpha}/{\beta}$ ratio (${\alpha}=0.0204,\;{\beta}=0.0334,\;R^2=0.999$, respectively). The SF curve from neutron beam had shoulders at low dose area and fitted well to LQ model with the value of $R^2$ exceeding 0.99 in all experiments. The mean value of alpha and beta were -0.315 (range, $-0.254{\sim}-0.360$) and 0.247 ($0.220{\sim}0.262$), respectively. The addition of lead shielding resulted in no straightening of SF curve and shoulders in low dose area still existed. The RBE of neutron beam was in range of $2.07{\sim}2.19$ with SF=0.1 and $2.21{\sim}2.35$ with SF=0.01, respectively. $\underline{Conclusion}$: The neutron beam from MC50 cyclotron has significant amount of gamma component and this may have contributed to form the shoulder of survival curve. The RBE of neutron beam generated by MC50 was about 2.2.
Youn Seon Min;Oh Young Kee;Kim Joo Heon;Park Mi Ja;Seong In Ock;Kang Kimun;Chai Gyuyong
Radiation Oncology Journal
/
v.23
no.1
/
pp.51-60
/
2005
Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.
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