Objectives : This study was aimed to define the protective effect of Tissue Cultured Root of Wild Ginseng (CWG) against doxorubicin (Doxo) toxicity, and investigate the anti-tumor synergic effect of CWG in combination with Doxo in tumor-bearing C57BL/6 mice. Methods : Tumor-bearing mice were established by single inoculation with B16/F10 melanoma cells (2$\times$10$^6$/ml) subcutaneously. Tumor-bearing mice (tumor volume between 50-100 mm$^3$) were selected and divided them into control, Doxo, and Doxo+CWG group. Mice of Doxo group were received with Doxo (4 mg/kg of B.W.) intraperitoneally at 0, 4, 8 days after starting the experiment. Mice of Doxo+CWG group were received CWG water extract during 12 days in combination with Doxo treatment. The body weight, tumor volume, tumor weight, and organ weight (heart, liver, kidney, and testis) were measured. And serum SPK, GOT and creatinine values were analysed. Results : The volume and weights of tumor masses in Doxo group were decreased significantly compared with the those of control group. And the those of Doxo+CWG group were not significantly different from the those of Doxo group. Whereas the weight of body, liver, kidney and testis in Doxo+CWG group were increased significantly compared with the those of Doxo group. The level of serum CPK and GOT in Doxo group were increased compared with the those of control group. But the value of Doxo+CWG group were decreased significantly compared with the values of Doxo group. Conclusions : These results suggest that CWG has protective effect against doxorubicin toxicity. And these effect is guessed that is caused in augmentation of vital energy.
Background: The impact of the immune response on cancer gene therapy using viral vectors to deliver a "suicide gene" is currently unclear. A vigrous immune response targeted at viral proteins or transgene may enhance the efficacy of tumor destruction and even augment responses to tumor antigens. These responses may involve the release of cytokines and stimulation of tumor specific cytotoxic T-lymphocytes that enhance therapeutic efficacy. On the other hand, a vigorous rapid cellular immune response may destroy cells expressing the therapeutic gene and attenuate the response to therapy. Furthermore, development of neutralizing antibody responses may prevent readministration of virus, a potentially significant limitation. Evaluating the significance of these limitations in animal models and developing solutions are therefore of obvious importance. Methods: After retroviral transduction of mouse mesothelioma cell line(AB12) with Herpes Simplex Virus thymidine kinase (HSVtk) gene in vitro, subcutaneous flank tumors were established. To study the effect of intact immune system on efficacy of tumor erradication, the ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Balb/c mice, immunodeficient Balb/c-nude and SCID mice, and Balb/c mice immunosuppressed with cyclosporin. Results: Ganciclovir treatment resulted in greater inhibition of tumor growth in Balb/c mice compared with immunodeficient Balb/c-nude mice and SCID mice(in immunodeficient mice, there were no growth inhibition by ganciclovir treatment). Ganciclovir treatment resulted in greater inhibition of tumor growth in noncyclosporin (CSA) treated Balb/c mice compared with CSA treated Balb/c mice. On day 8, mean ganciclovir-treated tumor volume were 65% of control tumor volume in Balb/c mice versus 77% control tumor volume in CSA-treated Balb/c mice. This effect was still evident during therapy (day 11 and 13). On day 13, non-CSA treated tumor volume was 35% of control tumor volume versus 60% of control tumor volume in CSA treated Balb/c mice. Duration of expression of HSVtk was not affected by the immunosuppression with CSA. Conclusion: These results indicate that the immune responses against retrovirally transduced cells enhance the efficacy of the HSVtk/ganciclovir system. These findings have important implications for clinical trials using currently available retrovirus vectors as well as for future vector design.
Kim, Hyun-Su;Wang, Ji-Hwan;Lim, Il-Hyuk;Park, Ki-Tae;Yeon, Seong-Chan;Lee, Hee-Chun
Journal of Veterinary Clinics
/
v.30
no.4
/
pp.268-272
/
2013
The purpose of this study was to assess the effects of reconstruction kernel, and slice thickness on the accuracy of spiral CT-based volume assessment over a range of object sizes typical of synthetic simulated tumor. Spiral CT scanning was performed at various reconstruction kernels (soft tissue, standard, bone), and slice thickness (1, 2, 3 mm) using a phantom made of gelatin and 10 synthetic simulated tumors of different sizes (diameter 3.0-12.0 mm). Three-dimensional volume assessments were obtained using an automated software tool. Results were compared with the reference volume by calculating the percentage error. Statistical analysis was performed using ANOVA and setting statistical significance at P < 0.05. In general, smaller slice thickness and larger sphere diameters produced more accurate volume assessment than larger slice thickness and smaller sphere diameter. The measured volumes were larger than the actual volumes by a common factor depending on slice thickness; in 100HU simulated tumors that had statistically significant, 1 mm slice thickness produced on average 27.41%, 2 mm slice thickness produced 45.61%, 3 mm slice thickness produced 93.36% overestimates of volume. However, there was no statistically significant difference in volume error for spiral CT scans taken with techniques where only reconstruction kernel was changed. These results supported that synthetic simulated tumor size, slice thickness were significant parameters in determining volume measurement errors. For an accurate volumetric measurement of an object, it is critical to select an appropriate slice thickness and to consider the size of an object.
Recently, MTV(metabolic tumor volume) has been used as indices of the whole tumor FDG uptake on FDG PET image but it is influenced by image reconstruction. The purpose of this study was to evaluate the correlation between actual volume and metabolic tumor volume applying different SUVmax threshold for different reconstruction algorithm on phantom study. Measurement were performed on a Siemens Biograph mCT40 using a NEMA IEC body phantom containing different size six spheres filled with F18-FDG applying four SBRs (4:1, 8:1, 10:1, 20:1). Images reconstructed four algorithms (OSEM3D, OSEM3D+PSF, OSEM3D +TOF, OSEM3D+TOF+PSF) and MTV were measured with different SUVmax threshold. Overall, the use of increasing thresholds result in decreasing MTV. and increasing the signal to background ratio decreased MTV by applying same SUVmax threshold. The 40% SUVmax threshold gave the best concordance between measured and actual volume in PSF and PSF+TOF reconstruction image. and the 45% threshold had the best correlation between the volume measured and actual volume in OSEM3D and TOF reconstruction image. we believe that this study will be used when the measurement of MTV applying various reconstruction image.
Kim, In-Young;Jung, Shin;Jung, Tae-Young;Moon, Kyung-Sub;Jang, Woo-Youl;Park, Jae-Young;Song, Tae-Wook;Lim, Sa-Hoe
Journal of Korean Neurosurgical Society
/
v.61
no.5
/
pp.633-639
/
2018
Objective : We investigated the outcomes of repeat stereotactic radiosurgery (SRS) for metastatic brain tumors that locally recurred despite previous SRS, focusing on the tumor control. Methods : A total of 114 patients with 176 locally recurring metastatic brain tumors underwent repeat SRS after previous SRS. The mean age was 59.4 years (range, 33 to 85), and there were 68 male and 46 female patients. The primary cancer types were non-small cell lung cancer (n=67), small cell lung cancer (n=12), gastrointestinal tract cancer (n=15), breast cancer (n=10), and others (n=10). The number of patients with a single recurring metastasis was 95 (79.8%), and another 19 had multiple recurrences. At the time of the repeat SRS, the mean volume of the locally recurring tumors was 5.94 mL (range, 0.42 to 29.94). We prescribed a mean margin dose of 17.04 Gy (range, 12 to 24) to the isodose line at the tumor border primarily using a 50% isodose line. Results : After the repeat SRS, we obtained clinical and magnetic resonance imaging follow-up data for 84 patients (73.7%) with a total of 108 tumors. The tumor control rate was 53.5% (58 of the 108), and the median and mean progression-free survival (PFS) periods were 246 and 383 days, respectively. The prognostic factors that were significantly related to better tumor control were prescription radiation dose of 16 Gy (p=0.000) and tumor volume less than both 4 mL (p=0.001) and 10 mL at the repeat SRS (p=0.008). The overall survival (OS) periods for all 114 patients after repeat SRS varied from 1 to 56 months, and median and mean OS periods were 229 and 404 days after the repeat SRS, respectively. The main cause of death was systemic problems including pulmonary dysfunction (n=58, 51%), and the identified direct or suspected brain-related death rate was around 20%. Conclusion : The tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors.
Recently, 18F-FDG PET based CT scan was a critical examination that the after, before plan diagnosis and treatment of tumors. But, due to the distortion of SUV that should be proportional to the metabolic rate of glucose in the tumor, the other measurement methods are being on study. In this study, compared the degree of distortion of SUV that according to the volume of the tumor analysis ROI and VOI using the NEMA IEC Phantom. The results, the SUVmax, mean value are rapidly decreased with threshold value 500 mm2 interval of the ROI analysis, 1500 mm3 interval of the VOI analysis. When compared SUVmax value SUVmean, ROI and VOI analysis VOI measurements was 1.077 times higher SUVmax was 0.981 times highe compared to the value of the ROI measurement. Compare MTV, SUV 2.0 as measured by the volume of the VOI to Volume showed a slightly higher results(Volume / MTV = $93.4 %{\pm}14.8 %$). Considering the above results, Tumor evaluation by 18F-FDG PET / CT scan Consider each threshold value should be analyzed due to larger SUV's Distortion depending on the size of the tumor. VOI analysis is recommended. because it showed the VOI analysis is higher than the ROI analysis SUVmax and lower SUVmean due to VOI analysis than once as a measure of the wider area as measured ROI analysis. MTV (R2 = 0.999), a result close to the actual size of the tumor. but, more research is needed in this regard, because SUV according to the standards of value are affected.
Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA, $100{\mu}g/100{\mu}l$) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume ($8.79{\pm}5.44$) and tumor burden ($3.60{\pm}1.17$). Comparatively, group III revealed only 20% of tumor incidence, tumor burden ($3.00{\pm}1.00$) and tumor volume ($2.40{\pm}1.12$), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.
Bae, Seon Yong;Park, Chul-Kee;Kim, Tae Min;Park, Sung-Hye;Kim, Il Han;Choi, Seung Hong
Investigative Magnetic Resonance Imaging
/
v.19
no.4
/
pp.218-223
/
2015
Purpose: To investigate whether volumetric analysis based on T2WI and contrast-enhanced (CE) T1WI can distinguish between isocitrate dehydrogenase-1 mutation-positive ($IDH1^P$) and -negative ($IDH1^N$) glioblastomas (GBMs). Materials and Methods: We retrospectively enrolled 109 patients with histopathologically proven GBMs after surgery or stereotactic biopsy and preoperative MR imaging. We measured the whole-tumor volume in each patient using a semiautomatic segmentation method based on both T2WI and CE T1WI. We compared the tumor volumes between $IDH1^P$ (n = 12) and $IDH1^N$ (n = 97) GBMs using an unpaired t-test. In addition, we performed receiver operating characteristic (ROC) analysis for the differentiation of $IDH1^P$ and $IDH1^N$ GBMs using the tumor volumes based on T2WI and CE T1WI. Results: The mean tumor volume based on T2WI was larger for $IDH1^P$ GBMs than $IDH1^N$ GBMs ($108.8{\pm}68.1$ and $59.3{\pm}37.3mm^3$, respectively, P = 0.0002). In addition, $IDH1^P$ GBMs had a larger tumor volume on CE T1WI than did $IDH1^N$ tumors ($49.00{\pm}40.14$ and $22.53{\pm}17.51mm^3$, respectively, P < 0.0001). ROC analysis revealed that the tumor volume based on T2WI could distinguish $IDH1^P$ from $IDH1^N$ with a cutoff value of 90.25 (P < 0.05): 7 of 12 $IDH1^P$ (58.3%) and 79 of 97 $IDH1^N$ (81.4%). Conclusion: Volumetric analysis of T2WI and CE T1WI could enable $IDH1^P$ GBMs to be distinguished from $IDH1^N$ GBMs. We assumed that secondary GBMs with $IDH1^P$ underwent stepwise progression and were more infiltrative than those with $IDH1^N$, which might have resulted in the differences in tumor volume.
Purpose: The enhanced cytotoxic effect of combined treatment of hyper-thermia and chemotherapy by increasing intracellular acidity with HMA was investigated. Materials and Methods: FSall tumor cells were injected on the hindlegs of female $C_3H$ mice. When the tumor volume reached about 200mm3, experiments were performed on the groups classified as follows: Group I :Control, Group II : Melphalan alone (2.5mg/kg, 5mg/kg, 10mg/kg, 15mg/kg), Group III : Heat alone $(42.5^{\cdot}C$ for 1 hour) Group IV : Melphalan + Heat $(42.5^{\cdot}C$ for 1 hour), Group V : HMA(10mg/kg) + Melphalan(5.0mg/kg) + Heat$(42.5^{\cdot}C$ for 1hour). Each group included 8-12 mice on each experiment HMA (3-amino-6-chloro-5-(1-homopiperidyl )-N-(diaminomethylene) -c-pyrazinecarboxamide), an analog of amiloride which increases intracellular pH(pHi) was dissolved in dimethyl sulfoxide (DMS) and injected into the tumor-bearing mice through the tail vein. 10mg/kg of HMA and each dose of melphalan were injected into peritoneum of the tumor-bearing mice 30 minutes before heating. Tumor growth delay was calculated when the tumor volme reached at $1500mm^3$ Excision assay was performed on each group and repeated 2-4 times. Results : Tumor growth delay of each experimental groups at $1500mm^3$ were 9, 10, 13 and 19 days respectively. In vivo-in vitro excision assay using FSall tumor cells, the cytotoxicity of each experimental groups was $1.2{\times}10^7,\;1{\times}10^7,\;6{\times}10^6,\;1.7{\times}10^6\;and\;1{\times}10^5$ clonogenic cells/gm respectively When HMA was added to the combined treatment of heat and .chemotherapy, the tumor growth was delayed more than combined treatment without HMA i.e., 6 days tumor growth delay at $1500mm^3$ of tumor volume. Conclusion: The combined effect of cytotoxicity by heat and chemotherapy can be much more enhanced by HMA.
Chang, Jong Hee;Chang, Jin Woo;Park, Yong Gou;Chung, Sang Sup
Journal of Korean Neurosurgical Society
/
v.30
no.5
/
pp.561-566
/
2001
Objective : The purpose of this study are to evaluate the effectiveness of Gamma Knife radiosurgery(GKS) as a treatment of craniopharyngioma and to investigate the proper dose planning technique in GKS for craniopharyngioma. Method : Between May 1992 and March 1999, seven Gamma Knife radiosurgical procedures were done for residual tumor mass of 6 patients with craniopharyngioma after microsurgical resection. Conventional radiation therapy was not performed. In this study, their clinical, radiological and radiosurgical data were analyzed and the radiation dosage to the optic pathway, hypothalamus, pituitary stalk, and cavernous sinus were calculated and correlation with clinical outcome was evaluated. The mean follow-up period was 33.5 months(12.3-55.2 months). Result : The mean tumor volume was 4.4cc(0.4-18.0cc) and the maximum radiation dose ranged from 14 to 32 Gy(mean 20.9Gy). The radiation was given with isodose curve, 50-90% and the marginal dose varied within 8-22.4Gy(mean 12.7Gy). The mean number of isocenter was 4.3(1-12). The tumor was well controlled in all cases. In 5 of 7 cases, the size of tumor decreased to 10-50% of pre-GKS volume and remaining two showed no volume change. The mean dose to optic pathway was 5.7Gy(5.1-11.2Gy) and there were no complications. Conclusion : GKS seems to be effective for control of craniopharyngioma as an adjuvant treatment after microsurgical resection and even suboptimal dose for tumor margin is considered to be enough for tumor control. It is safe with careful dose planning to protect surrounding important structures, especially optic pathway. We believe conventional radiation therapy should be avoided because it has limitation for dose planning of additional treatments such as radiosurgery or intracystic instillation of radioisotope in case of recurrence.
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