• Radiation Oncology Journal
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• v.26 no.2
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• pp.104-112
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• 2008

Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.1
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• pp.127-135
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• 2014

Purpose : By taking advantage of each imaging modality, the use of fused CT/MRI image has increased in prostate cancer radiation therapy. However, fusion uncertainty may cause partial target miss or normal organ overdose. In order to complement such limitation, our hospital acquired MRI image (Planning MRI) by setting up patients with the same fixing tool and posture as CT simulation. This study aims to evaluate the usefulness of the Planning MRI through comparing and analyzing the diagnostic MRI image and Planning MRI image. Materials and Methods : This study targeted 10 patients who had been diagnosed with prostate cancer and prescribed nonhormone and definitive RT 70 Gy/28 fx from August 2011 to July 2013. Each patient had both CT and MRI simulations. The MRI images were acquired within one half hour after the CT simulation. The acquired CT/MRI images were fused primarily based on bony structure matching. This study measured the volume of prostate in the images of Planning MRI and diagnostic MRI. The diameters at the craniocaudal, anteroposterior and left-to-right directions from the center of prostate were measured in order to compare changes in the shape of prostate. Results : As a result of comparing the volume of prostate in the images of Planning MRI and diagnostic MRI, they were found to be $25.01cm^3$(range $15.84-34.75cm^3$) and $25.05cm^3$(range $15.28-35.88cm^3$) on average respectively. The diagnostic MRI had an increase of 0.12 % as compared with the Planning MRI. On the planning MRI, there was an increase in the volume by $7.46cm^3$(29 %) at the transition zone directions, and there was a decrease in the volume by $8.52cm^3$(34 %) in the peripheral zone direction. As a result of measuring the diameters at the craniocaudal, anteroposterior and left-to-right directions in the prostate, the Planning MRI was found to have on average 3.82cm, 2.38cm and 4.59cm respectively and the diagnostic MRI was found to have on average 3.37cm, 2.76cm and 4.51cm respectively. All three prostate diameters changed and the change was significant in the Planning MRI. On average, the anteroposterior prostate diameter decrease by 0.38cm(13 %). The mean right-to-left and craniocaudal diameter increased by 0.08cm(1.6 %) and 0.45cm(13 %), respectively. Conclusion : Based on the results of this study, it was found that the total volumes of prostate in the Planning MRI and the diagnostic MRI were not significantly different. However, there was a change in the shape and partial volume of prostate due to the insertion of prostate balloon tube to the rectum. Thus, if the Planning MRI images were used when conducting the fusion of CT/MRI images, it would be possible to include the target in the CTV without a loss as much as the increased volume in the transition zone. Also, it would be possible to reduce the radiation dose delivered to the rectum through separating more clearly the reduction of peripheral zone volume. Therefore, the author of this study believes that acquisition of Planning MRI image should be made to ensure target delineation and localization accuracy.

• The Journal of Korean Society for Radiation Therapy
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• v.17 no.2
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• pp.133-140
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• 2005

Purpose : This test is designed to identify the validity of treatment plan by implementing real-time dosimetry by means of dose that is absorbed into PTV and OAR when preparing doses of 3D and POP plans. Materials and Methods : In treatment. error can be calculated be comparing Exp. Dose with the actual dose, which has been converted from 'the reading value obtained by placing diode detector on the area to be measured'. Same test can be repeated using Alderson-Rando phantom. Results : Errors were found: A patient(POP plan): 197.6/199=-1.2%, B patient(3D-plan): 199.9/198.7=+0.6%, C patient: 196/200=-1.5%. In addition, considering the resulted value of measuring OAR besides target-dose for C patient showed 96/200, representing does of 47%, the purpose of protection was judged to be duly accomplished. Also it was acknowledged the resulted value of -3.7% met the targeted dose within the range of ${\pm}5%$. Conclusion : Aimed for identifying the usefulness of pre-treatment dose measurement using diode detector, this test was useful to evaluate the validity of curing because it resulted in the identification of category to be protected as well as t dose. Moreover, it is thought to have great advantage in ascertaining the dose of target, dose of which is not calculated yet. Similar to L-gram before treatment, this test is thought to be very effective so that it can bring great advantages in the aspects such as validity of curing method and post-treatment plan as well.

• Journal of Life Science
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• v.26 no.1
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• pp.23-33
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• 2016

Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. The purpose of this study was to develop methods to maximize the stability of Pexa-Vec. In short-term instability testing, viral activity was rapidly decreased both at 4℃ and at room temperature (RT), but it was completely restored after sonication followed by vortex. Long-term stability testing of Pexa-Vec in the following liquid formulations was performed: (A) 30 mM Tris/pH 7.6, (B) 30 mM Tris/pH 8.6, (C) 30 mM Tris/pH 7.6, 150 mM NaCl, 15% sucrose, (D) 30 mM Tris/pH 7.6, 15% sucrose, and (E) 30 mM Tris/pH 8.6, 15% sucrose. Viral activity decreased less than 2 log10 at 4℃, and RT was observed in 3 days in B, while viral activity was not decreased even after 4–8 weeks at 4℃ and at 1 week in RT in A, suggesting that neutral pH may be essential to maintain virus stability. The addition of 15% sucrose into A (D) significantly increased viral stability at −20℃, 4℃, or RT, and it was also observed at pH 8.6 (E). The addition of 150 mM NaCl into D (C) significantly increased viral stability in addition to the sucrose effect at 4℃ or RT. Accordingly, the viral activity in formulation C was maintained for 1.5 years at 4℃, and for 1-2 weeks in RT. In conclusion, we propose that formulation C can provide the most adequate condition for the proper storage of vaccinia oncolytic virus.

• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.11-20
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• 2011

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.916-924
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• 1996

Bacground : Percutaneous needle aspiration biopsy (PCNA) is one of the most frequently used diagnostic methcxJs for intrathoracic lesions. Previous studies have reponed wide range of diagnostic yield from 28 to 98%. However, diagnostic yield has been increased by accumulation of experience, improvement of needle and the image guiding systems. We analysed the results of PCNA performed for one year to evaluate the diagnostic yield, the rate and severity of complications and factors affecting the diagnostic yield. Method : 287 PCNAs undergone in 236 patients from January, 1994 to December, 1994 were analysed retrospectively. The intrathoracic lesions was targeted and aspirated with 21 - 23 G Chiba needle under fluoroscopic guiding system. Occasionally, 19 - 20 G Biopsy gun was used for core tissue specimen. The specimen was requested for microbiologic, cytologic and histopathologic examination in the case of obtained core tissue. Diagnostic yields and complication rate of benign and malignant lesions were ca1culaled based on patients' chans. The comparison for the diagnostic yields according to size and shape of the lesions was analysed with chi square test (p<0.05). Results : There are 19.9% of consolidative lesion and 80.1% of nodular or mass lesion, and the lesion is located at the right upper lobe in 26.3% of cases, the right middle lobe in 6.4%, the right lower lobe 21.2%, the left upper lobe in 16.8%, the left lower lobe in 10.6%, and mediastinum in 1.3%. The lesion distributed over 2 lobes is as many as 17.4% of cases. There are 74 patients with benign lesions, 142 patients with malignant lesions in final diagnosis and confirmative diagnosis was not made in 22 patients despite of all available diagnostic methods. 2 patients have lung cancer and pulmonary tuberculosis concomittantly. Experience with 236 patients showed that PCNA can diagnose benign lesions in 62.2% (42 patients) of patients with such lesions and malignant lesions in 82.4% (117 patients) of patients. For the patients in whom the first PCNA failed to make diagnosis, the procedure was repeated and the cumulative diagnostic yield was increased as 44.6%, 60.8%, 62.2% in benign lesions and as 73.4%, 81.7%, 82.4% in malignant lesions through serial PCNA. Thoracotomy was performed in 9 patients with benign lesions and in 43 patients with malignant lesions. PCNA and thoracotomy showed the same pathologic result in 44.4% (4 patients) of benign lesions and 58.1% (25 patients) of malignant lesions. Thoracotomy confirmed 4 patients with malignat lesions against benign result of PCNA and 2 patients with benign lesions against malignant result of PCNA. There are 1.0% (3 cases) of hemoptysis, 19.2% (55 cases) of blood tinged sputum, 12.5% (36 cases) of pneumothorax and 1.0% (3 cases) of fever through 287 times of PCNA. Hemoptysis and blood tinged sputum didn't need therapy. 8 cases of pneumothorax needed insertion of classical chest tube or pig-tail catheter. Fever subsided within 48 hours in all cases. There was no difference between size and shape of lesion with diagnostic yield. Conclusion: PCNA shows relatively high diagnostic yield and mild degree complications but the accuracy of histologic diagnosis has to be improved.