• Progress in Medical Physics
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• v.16 no.1
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• pp.24-31
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• 2005

The stereotactic radiosurgery (SRS) describes a method of delivering a high dose of radiation to a small tar-get volume in the brain, generally in a single fraction, while the dose delivered to the surrounding normal tissue should be minimized. To perform automatic plan of the SRS, a new method of multi-isocenter/shot linear accelerator (linac) and gamma knife (GK) radiosurgery treatment plan was developed, based on a physical lattice structure in target. The optimal radiosurgical plan had been constructed by many beam parameters in a linear accelerator or gamma knife-based radiation therapy. In this work, an isocenter/shot was modeled as a sphere, which is equal to the circular collimator/helmet hole size because the dimension of the 50% isodose level in the dose profile is similar to its size. In a computer-aided system, it accomplished first an automatic arrangement of multi-isocenter/shot considering two parameters such as positions and collimator/helmet sizes for each isocenter/shot. Simultaneously, an irregularly shaped target was approximated by cubic structures through computation of voxel units. The treatment planning method by the technique was evaluated as a dose distribution by dose volume histograms, dose conformity, and dose homogeneity to targets. For irregularly shaped targets, the new method performed optimal multi-isocenter packing, and it only took a few seconds in a computer-aided system. The targets were included in a more than 50% isodose curve. The dose conformity was ordinarily acceptable levels and the dose homogeneity was always less than 2.0, satisfying for various targets referred to Radiation Therapy Oncology Group (RTOG) SRS criteria. In conclusion, this approach by physical lattice structure could be a useful radiosurgical plan without restrictions in the various tumor shapes and the different modality techniques such as linac and GK for SRS.

• The Journal of Korean Society for Radiation Therapy
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• v.33
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• pp.35-46
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• 2021

Purpose : By comparing and analyzing treatment plans using abdominal compression and The Continuous Positive Air Pressure(CPAP) during SABR of lung cancer, we try to contribute to the improvement of radiotherapy effect. Materials & Methods : In two of the lung SABR patients(A, B patient), we developed a SABR plan using abdominal compression device(the Body Pro-Lok, BPL) and CPAP and analyze the treatment plan through homogeneity, conformity and the parameters proposed in RTOG 0813. Furthermore, for each phase, the X, Y, and Z axis movements centered on PTV are analyzed in all 4D CTs and compared by obtaining the volume and average dose of PTV and OAR. Four cone beam computed tomography(CBCT) were used to measure the directions from the center of the PTV to the intrathoracic contacts in three directions out of 0°, 90°, 180° and 270°, and compare the differences from the average distance values in each direction. Result : Both treatment plans obtained using BPL and CPAP followed recommendations from RTOG, and there was no significant difference in homogeneity and conformity. The X-axis, Y-axis, and Z-axis movements centered on PTV in patient A were 0.49 cm, 0.37 cm, 1.66 cm with BPL and 0.16 cm, 0.12 cm, and 0.19 cm with CPAP, in patient B were 0.22 cm, 0.18 cm, 1.03 cm with BPL and 0.14 cm, 0.11 cm, and 0.4 cm with CPAP. In A patient, when using CPAP compared to BPL, ITV decreased by 46.27% and left lung volume increased by 41.94%, and average dose decreased by 52.81% in the heart. In B patient, volume increased by 106.89% in the left lung and 87.32% in the right lung, with an average dose decreased by 44.30% in the stomach. The maximum difference of A patient between the straight distance value and the mean distance value in each direction was 0.05 cm in the a-direction, 0.05 cm in the b-direction, and 0.41 cm in the c-direction. In B patient, there was a difference of 0.19 cm in the d-direction, 0.49 cm in the e-direction, and 0.06 cm in the f-direction. Conclusion : We confirm that increased lung volume with CPAP can reduce doses of OAR near the target more effectively than with BPL, and also contribute more effectively to restriction of tumor movement with respiration. It is considered that radiation therapy effects can be improved through the application of various sites of CPAP and the combination with CPAP and other treatment machines.

• Journal of Radiation Protection and Research
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• v.28 no.3
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• pp.225-231
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• 2003

Up-front irradiation technique as 3-dimensional conformation, or intensity modulation has kept large proportion of brain tumors from being complicated with acute radiation reactions in the normal tissue during or shortly after radiotherapy. For years, we've cannot help but counting on 2-D vertex beam technique to reduce acute reactions in the brain tumor patients because we're not equipped with 3-dimensional planning system. We analyzed its advantages and limitations in the clinical application. From 1998 to 2001, vertex or oblique vertex beams were applied to 35 patients with primary brain tumor and 25 among them were eligible for this analysis. Vertex(V) plans were optimized on the reconstructed coronal planes. As the control, we took the bilateral opposed techniques(BL) otherwise being applied. We compared the volumes included in 105% to 50% isodose lines of each plan. We also measured the radiation dose at various extracranial sites with TLD. With vertex techniques, we reduced the irradiated volumes of contralateral hemisphere and prevented middle ear effusion at contralateral side. But the low dose volume increased outside 100%; the ratio of V to BL in irradiated volume included in 100%, 80%, 50% was 0.55+/-0.10, 0.61+/-0.10, and 1.22+/-0.21, respectively. The hot area within 100% isodose line almost disappeared with vertex plan; the ratio of V to BL in irradiated volume included in 103%, 105%, 108% was 0.14+/-0.14, 0.05./-0.17, 0.00, respectively. The dose distribution within 100% isodose line became more homogeneous; the ratio of volume included in 103% and 105% to 100% was 0.62+/-0.14 and 0.26+/-0.16 in BL whereas was 0.16+/-0.16 and 0.02+/-0.04 in V. With the vertex techniques, extracranial dose increased up to $1{\sim}3%$ of maximum dose in the head and neck region except submandibular area where dose ranged 1 to 21%. From this data, vertex beam technique was quite effective in reduction of unnecessary irradiation to the contralateral hemispheres, integral dose, obtaining dose homogeneity in the clinical target. But it was associated with volume increment of low dose area in the brain and irradiation toward the head and neck region otherwise being not irradiated at all. Thus, this 2-D vertex technique can be a useful quasi-conformal method before getting 3-D apparatus.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6749-6754
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• 2014

Background: There are limited data in the literature related to concomitant genital or extra-genital organ pathologies in patients with borderline ovarian tumors (BOTs). The aim of this study was to evaluate our experience with 183 patients to draw attention to the accompanying organ pathologies with BOTs. Materials and Methods: One hundred eighty-three patients with BOTs, diagnosed and/or treated in our center between January of 2000 and March of 2013 were evaluated retrospectively. Data related to age, tumor histology, lesion side, disease stage, accompanying incidental ipsilateral and/or contralateral ovarian pathologies, treatment approaches, and follow-up periods were investigated. Incidental gynecologic and non-gynecologic concomitant organ pathologies were also recorded. Results: The mean age at diagnosis was 40.6 years (range: 17-78). Ninety-five patients (51%) were ${\leq}40$ years. A hundred and forty-seven patients (80%) were at stage IA of the disease. The most common type of BOT was serous in histology. Non-invasive tumor implants were diagnosed in 4% and uterine involvement was found 2% among patients who underwent hysterectomies. There were 12 patients with positive peritoneal washings. Only 17 and 84 patients respectively had concomitant ipsilateral and concomitant contralateral incidental ovarian pathologies. The most common type of uterine, appendicular and omental pathologies were chronic cervicitis, lymphoid hyperplasia and chronic inflammatory reaction. Conclusions: According to our findings most of accompanying pathologies for BOT are benign in nature. Nevertheless, there were additional malignant diseases necessitating further therapy. We emphasize the importance of the evaluation of all abdominal organs during surgery.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4969-4976
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• 2014

Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6605-6611
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• 2013

Background: WEE1 is a G2/M checkpoint regulator protein. Various studies have indicated that WEE1 could be a good target for cancer therapy. The main aim of this study was to asssess the tumor suppressive potential of WEE1 silencing in two different breast cancer cell lines, MCF7 which carries the wild-type p53 and MDA-MB468 which contains a mutant type. Materials and Methods: After WEE1 knockdown with specific shRNAs downstream effects on cell viability and cell cycle progression were determined using MTT and flow cytometry analyses, respectively. Real-time PCR and Western blotting were conducted to assess the effect of WEE1 inhibition on the expression of apoptotic (p53) and anti-apoptotic (Bcl2) factors and also a growth marker (VEGF). Results: The results showed that WEE1 inhibition could cause a significant decrease in the viability of both MCF7 and MDA-MB-468 breast cancer cell lines by more than 50%. Interestingly, DNA content assays showed a significant increase in apoptotic cells following WEE1 silencing. WEE1 inhibition also induced upregulation of the apoptotic marker, p53, in breast cancer cells. A significant decrease in the expression of VEGF and Bcl-2 was observed following WEE1 inhibition in both cell lines. Conclusions: In concordance with previous studies, our data showed that WEE1 inhibition could induce G2 arrest abrogation and consequent cell death in breast cancer cells. Moreover, in this study, the observed interactions between the pro- and anti-apoptotic proteins and decrease in the angiogenesis marker expression confirm the susceptibility to apoptosis and validate the tumor suppressive effect of WEE1 inhibition in breast cancer cells. Interestingly, the levels of the sensitivity to WEE1 silencing in breast cancer cells, MCF7 and MDA-MB468, seem to be in concordance with the level of p53 expression.

• Journal of Life Science
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• v.26 no.1
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• pp.91-100
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• 2016

Angiogenesis is essential for the pathophysiological processes of embryogenesis, tissue growth, diabetic retinopathy, psoriasis, wound healing, rheumatoid arthritis, cardiovascular diseases, and tumor growth. Inhibition of angiogenesis represents an attractive therapeutic approach for the treatment of angiogenic diseases such as cancer. However, uncontrolled angiogenesis is also necessary for tumor development and metastasis. Inhibition of vascular endothelial growth factor (VEGF) signaling, a critical factor in the induction of angiogenesis, cause robust and rapid changes in blood vessels of tumors and therefore VEGF constitutes a target for such anti-angiogenic therapy. Recently, since natural compounds pose significantly less risk of deleterious side effects than synthetic compounds, a great many natural resources have been assessed for useful substance for anti-angiogenic treatment. Here we evaluated the anti-angiogenic effects of a hot water extract of Scutellaria baicalensis (SBHWE) using in vitro assays and ex vivo animal experiments. Our results show that SBHWE dose-dependently abrogated vascular endothelial responses by inhibiting VEGF-stimulated migration and invasion as well as tube formation in a human umbilical vein endothelial cell (HUVEC) model, without cytotoxicity, as determined by a cell viability assay. Further study revealed that SBHWE prevented VEGF-induced neo-vascularization in a rat aortic ring sprouting model. Taken together, our findings reveal an anti-angiogenic activity of Scutellaria baicalensis and suggest that SBHWE is a novel candidate inhibitor of VEGF-induced angiogenesis.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.274-283
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• 2022

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

• Journal of Veterinary Science
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• v.25 no.1
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• pp.15.1-15.15
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• 2024

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.339-346
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• 1999

Background : Non-small cell lung carcinoma is a common tumor with a poor prognosis. Of all malignancies, it is the main cause of death for male and female patients in the Western world. Resection remains the most effective treatment when feasible. Accurate description and classification of the extent of cancer growth are important in planning treatment, estimating prognosis, evaluating end results of therapy, and exchanging information on human cancer research. Until effective systemic therapy is available for non-small cell lung cancer, development of new treatment strategies depends on knowledge of the end results achieved for carefully staged groups of patients in the lung cancer populations. For these reasons, we investigated the survival rate in radically resected non-small cell lung cancer patients by newly revised staging system adopted by the American Joint Committee on Cancer and the Union Internationale Contre le Cancer. Methods: Clinical, surgical-pathologic and follow-up informations on 84 consecutive, previously untreated, patients who received their primary treatment for non-small cell lung cancer were investigated. Staging definitions for the T(primary tumor), N(reginal lymph node), and M(distant metastasis) components were according to the International Staging System for Lung Cancer. Death from any causes was the primary target of the evaluation. Results: The median survival rates were as follows; stage I ;79.1 months, stage II ;47.3 months, stage IIIa; 22.7 months, stage IIIb; 16.1 months, and stage IV;15.2 months versus newly revised stage Ia;58.5 months, stage I b;76.0 months, stage IIa; not available, stage IIb;43.0 months, stage IIIa;22.5 months, stage IIIb; 16.1 months, and stage IV;15.2 months. The survival rates were not significantly different between old and newly revised staging system. Cumulative percent survival at 36months after treatment was 100% in stage Ia, 80% in stage Ib, not available in stage IIa, 26 % in stage IIb, and 21 % in stage m a respectively. Conclusions: Although these data were not significantly different statistically, the newly revised lung cancer staging system might be more promising for the accurate evaluation of the prognosis in the non-small cell lung caner patients.