• The Journal of Korean Society for Radiation Therapy
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• v.30 no.1_2
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• pp.17-25
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• 2018

Purpose : To compare the radiation doses of prostate cancer patients according to changes in abdominal body shape and energy during Volumetric modulated arc therapy(VMAT). Materials and Methods : Seven patients with prostate cancer were enrolled in this study. VMAT treatment plan was established at 6, 10, and 15 MV while changing from -2.0 cm to 2 cm by 0.5 cm. Conformal index(CI), homogeneous index(HI), $D_{max}$, $D_{95%}$, $D_{50%}$ and $D_{2%}$ of PTV were examined in order to evaluate the change of dose in the target organ according to body shape change. Normal organ of the femoral head, rectum and bladder was analyzed to evaluate dose changes. Results : The dose of $D_{max}$ 6 MV in PTV increased to 107.2 % in 1.0 cm body shape reduction, and 10 MV and 15 MV dose increased to 107.1 % and 107.0 % in 1.5 cm body reduction, respectively. The dose of $D_{50%}$ 6 MV in PTV decreased to 99.64 % in 1.0 cm body shape increase, and in 10 MV and 15 MV dose decreased to 99.79 % and 99.97 % in 1.5 cm body increase, respectively. In 2.0 cm body type increase, the dose was decreased to 99.30 % and 99.52 %, respectively. Doses for rectum and bladder gradually increased with decreasing weight, and dose decreased with decreasing weight. 6 MV, and $V_{70Gy}$ at 10 MV increased from 11.50 % to 12.76 % when the external shape decreased by 2.0 cm. The bladder $V_{70Gy}$ also increased from 14.0 % to 15.2 %. It was also shown that the dose increased as the body weight decreased in the femoral head. Conclusion : In the treatment of VMAT, dose distribution can be changed according to the change of abdominal shape. SSD and CBCT were used to decrease the body shape by more than 1cm or more than 1.0 cm at 6 MV and the body shape by more than 1.5 cm or more than 1.5 cm at 10 MV or 15 MV. It is considered that a new treatment plan should be established through re-simulation.

• Journal of Life Science
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• v.29 no.8
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• pp.904-915
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• 2019

Prostate cancer (PCa) is one of the most metastatic tumor. Although hormone therapy or surgical castration is mostly conducted to treat PCa, it has a lot of side effects. Recently, many researchers have been exploring the tumor microenvironment to remedy these circumstances. Immune cells, especially macrophages, are an important composition of the tumor microenvironment. Under normal conditions, macrophages exhibit mild tumoricidal activity against tumors. However, once activated by interferon gamma or lipopolysaccharides, macrophages can kill cancer cells directly or indirectly by secreting cytokines and chemokines. In this study, murine macrophage RAW 264.7 cells were treated with Phellinus linteus extract. To analyze their pro-inflammatory phenotype, we were used several assays such as a real-time polymerase chain reaction, an enzyme-linked immunosorbent and nitric oxide assay. Prostate cancer cells were treated with the RAW 264.7-conditioned media, which was identified as a pro-inflammatory nature, for 48 h, and the expression of epithelial-mesenchymal transition (EMT)-related genes was determined. Not only N-cadherin, Snail, Twist, Slug, and Cadherin 11, which are mechenchymal-related proteins, were decrease, but epithelial marker of E-cadherin was increased. In addition, the mRNA level of vimentin, ccl2, and vegfa were decreased, as the EMT is closely related to the migration and invasion of cancer cells. In conclusion, the RAW 264.7-conditioned media stimulated with P. linteus extract inhibited migration and invasion and regulated the EMT pathway in human prostate cancer cells.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.534-546
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• 1997

Background : The p53 and retinoblastoma(Rb) tumor suppressor genes are associated with the pathogenesis of several types of human cancer. Substantial proportion of the primary lung cancers or cell lines have been reported to have the p53 and/or the Rb gene mutations. But, so far there is no report on the analysis of the Rb gene polymorphism as one of the genetic susceptibility marker. This study was undertaken to establish the gene frequencies of the polymorphic genotypes of the p53 and Rb genes in Koreans to evaluate the possible involvement of these genotypes as a risk factor of lung cancer. Methods : In this study 145 controls without previous and present tumor history and 128 lung cancer patients were subjected to analysis. The two intragenic polymorphisms of the p53 gene(exon 4/ AccII, intron 6/MspI) and one intron 17/XbaI polymorphism of the Rb gene were analysed by the method of polymersae chain reaction- restriction fragment length polymorphisms(PCR-RFLPs). The genotype of the intron 3/16 bp repeat polymorphism of p53 was determined by PCR and direct gel electrophoresis. Results : There were no significant differences in the genotype distributions of the p53 gene between lung cancer patients and controls. But heterozygotes(Arg/Pro) of the exon 4/AccII polymorphisms were slightly over-represented than controls, especially in the Kreyberg type I cancer, which was known to be associated with smoking. The intron 3/16 bp duplication and the intron 6/MspI polymorphisms were in complete linkage disequilibrium. About 95% of the individuals were homozygotes of the common alleles both in the 16 duplication and MspI polymorphisms, and no differences were deteced in the genotype distributions between lung cancer patients and controls. Overall genotype distributions of the Rb gene polymorphisms between lung cancer patients and controls were not significantly different However, the genotype distributions in the Kreyberg type I cancer were significantly different from those of controls(p = 0.0297) or adenocarcinomas(p = 0.0008). It was noticeable that 73.4% of the patients with adenocarcinomas were heterozygotes(r1/r2) whereas 39.2% of the Kreyberg type I cancer were heterozygous at this polymorphisms. In the lung cancer patients, significant differences were also noted between the high dose smokers and low dose smokers including non-smokers(p = 0.0258). The relative risk to Kreyberg type I cancer was significantly reduced in the individuals with the genotype of r1/r2(odds ratio = 0.46, 95% C.I. = 0.25-0.86, p = 0.0124). The combined genotype distribution of the exon 4 AccII of the p53 and the intron 17 Rb gene polymorphisms in Kreyberg type I cancers were significantly different from dose of controls or adenocarcinomas. The highest odds ratio were observed in the individuals with the genotypes of Arg/Pro and r2/r2(odds ratio = 1.97,95% C.I. = 0.84-4.59) and lowest one was in the patients with Arg/Arg, r1/r2 genotype(odds ratio = 0.54, 95% C.I. = 0.25-1.14). Conclusion : The p53 and the Rb gene polymorphisms modulate the risk of smoking induced lung cancer development in Koeans. However, the exact mechanism of risk modulation by these polymorphism remains to be determined. For more discrete clarification of associations between specific genotypes and lung cancer risk, the evaluations of these polymorphisms in other ethnics and more number of patients will be needed.

• The Journal of Korean Society for Radiation Therapy
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• v.27 no.2
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• pp.131-143
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• 2015

Purpose : By comparing a CT fusion plan based on MRI with a plan based on only MRI without CT, we intended to study usefulness of a plan based on only MRI. And furthermore, we intended to realize a realtime MR-IGRT by MRI image without CT scan during the course of simulation, treatment planning, and radiation treatment. Materials and Methods : BBB CT (Brilliance Big Bore CT, 16slice, Philips), Viewray MRIdian system (Viewray, USA) were used for CT & MR simulation and Treatment plan of 11 patients (1 Head and Neck, 5 Breast, 1 Lung, 3 Liver, 1 Prostate). When scanning for treatment, Free Breathing was enacted for Head&Neck, Breast, Prostate and Inhalation Breathing Holding for Lung and Liver. Considering the difference of size between CT and Viewray, the patient's position and devices were in the same condition. Using Viewray MRIdian system, two treatment plans were established. The one was CT fusion treatment plan based on MR image. Another was MR treatment plan including electron density that [ICRU 46] recommend for Lung, Air and Bone. For Head&Neck, Breast and Prostate, IMRT was established and for Lung and Liver, Gating treatment plan was established. PTV's Homogeneity Index(HI) and Conformity Index(CI) were use to estimate the treatment plan. And DVH and dose difference of each PTV and OAR were compared to estimate the treatment plan. Results : Between the two treatment plan, each difference of PTV's HI value is 0.089% (Head&Neck), 0.26% (Breast), 0.67% (Lung), 0.2% (Liver), 0.4% (Prostate) and in case of CI, 0.043% (Head&Neck), 0.84% (Breast), 0.68% (Lung), 0.46% (Liver), 0.3% (Prostate). As showed above, it is on Head&Neck that HI and CI's difference value is smallest. Each difference of average dose on PTV is 0.07 Gy (Head&Neck), 0.29 Gy (Breast), 0.18 Gy (Lung), 0.3 Gy (Liver), 0.18 Gy (Prostate). And by percentage, it is 0.06% (Head&Neck), 0.7% (Breast), 0.29% (Lung), 0.69% (Liver), 0.44% (Prostate). Likewise, All is under 1%. In Head&Neck, average dose difference of each OAR is 0.01~0.12 Gy, 0.04~0.06 Gy in Breast, 0.01~0.21 Gy in Lung, 0.06~0.27 Gy in Liver and 0.02~0.23 Gy in Prostate. Conclusion : PTV's HI, CI dose difference on the Treatment plan using MR image is under 1% and OAR's dose difference is maximum 0.89 Gy as heterogeneous tissue increases when comparing with that fused CT image. Besides, It characterizes excellent contrast in soft tissue. So, radiation therapy using only MR image without CT scan is useful in the part like Head&Neck, partial breast and prostate cancer which has a little difference of heterogeneity.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.310-322
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• 2000

Background : Phospholipase C(PLC) plays an important role in cellular signal transduction and is thought to be critical in cellular growth, differentiation and transformation of certain malignancies. Two second messengers produced from the enzymatic action of PLC are diacylglycerol (DAG) and inositol 1, 4, 5-trisphosphate (IP3). These two second messengers are important in down stream signal activation of protein kinase C and intracellular calcium elevation. In addition, functional domains of the PLC isozymes, such as Src homology 2 (SH2) domain, Src homology 3 (SH3) domain, and pleckstrin homology (PH) domain play crucial roles in protein translocation, lipid membrane modificailon and intracellular memrane trafficking which occur during various mitogenic processes. We have previously reported the presence of PLC-${\gamma}1$, ${\gamma}2$, ${\beta}1$, ${\beta}3$, and ${\delta}1$ isozymes in normal human lung tissue and tyrosine-kinase-independent activation of phospholipase C-${\gamma}$ isozymes by tau protein and AHNAK. We had also found that the expression of AHNAK protein was markedly increased in various mstologic types of lung can∞r tissues as compared to the normallungs. However, the report concerning expression of various PLC isozymes in lung canærs and other lung diseases is lacking. Therefore, in this study we examined the expression of PLC isozymes in the paired surgical specimens taken from lung cancer patients. Methods : Surgically resected lung cancer tissue samples taken from thirty seven patients and their paired normal control lungs from the same patients, The expression of various PLC isozymes were studied. Western blot analysis of the tissue extracts for the PLC isozymes and immunohistochemistry was performed on typical samples for localization of the isozyme. Results : In 16 of 18 squamous cell carcinomas, the expression of PLC-${\gamma}1$ was increased. PLC-${\gamma}1$ was also found to be increased in all of 15 adenocarcinoma patients. In most of the non-small cell lung cancer tissues we had examined, expression of PLC-${\delta}1$ was decreased. However, the expression of PLC-${\delta}1$ was markedly increased in 3 adenocarcinomas and 3 squamous carcinomas. Although the numbers were small, in all 4 cases of small cell lung cancer tissues, the expression of PLC-${\delta}1$ was nearly absent. Conclusion : We found increased expression of PLC-${\gamma}1$ isozyme in lung cancer tissues. Results of this study, taken together with our earlier findings of AHNAK protein-a putative PLD-${\gamma}$, activator-over-expression, and the changes observed in PLC-${\delta}1$ in primary human lung cancers may provide a possible insight into the derranged calcium-inositol signaling pathways leading to the lung malignancies.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.121-128
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• 1997

Purpose : To evaluate the effect of postoperative adjuvant radiation therapy and chemotherapy on the survival, pattern of failure and complication for locally advanced rectal carcinoma Materials and Methods : From October 1992 to September 1995, twenty eight patients with rectal carcinoma were treated by postoperative adjuvant radiation therapy and chemotherapy Radiation therapy was delivered with 6MV and 15MV linear accelerator, 180c0y fractions 5 day per week. Total radiation doses were 5040cGy in $B_{2+3}$ and 5580cGy in $C_{2+3}$. Within 4 weeks after radical surgery. 5-FU$(400mg/m^2/day)\;and\;Leucovorin(20mg/m^2/day)$ were administered by intravenous injection for 4 days during the first and fifth week of radiation therapy. The median follow up was 19 months with a range 2 to 47 months. Results : The 2 year overall survival and disease free survival rates were $78.6\%\;and\;70.8\%$, respectively. The 2 year overall survival was $93.0\%\;in\;B_{2+3}$ and $76.2\%\;in\;C_{2+3}$(p=0.11) The 2 year disease free survival was $79.4\%\;in\;B_{2+3}\;and\;69.2\%\;in\;C_{2+3}(p=0.13)$. The overall failure rate was $21.42\%$(6/28) including $10.72\%$(3/28) locoregional recurrence, $3.62\%$(1/28) distant metastasis and $7.12\%$(2/28) locoregional recurrence with distant metastasis. The overall locoregional recurrence rate was $17.92\%$(5/28). The 2 year locoregional recurrence rates were $13.32\%(2/15)\;and\;23.12\%$(3/13) for respectively for $B_{2+3}\;and\;C_{2+3}$ The difference between the locoregional recurrence of $B_{2+3}\;and\;C_{2+3}$ patients was not significant(p=0.07). Complications developed in 13 patients$(46.42\%)$, including 8 dermatitis, 7 loose stool, 6 leukopenia, 4 tenesmus, 2 diarrhea. In Univariate analysis, there was no statistically significant factor except for tumor grade in locoregional recurrence, disease free survival and overall survival rate(p=0.04, 0.05, 0.04). Conclusion : This study sugges1s that postoperative adjuvant radiation therapy and chemotherapy is effective in patients with locally advanced rectal cancer. Therefore these results need to be confirmed with a long term follow-up and larger number of patients with the further clinical trials including prospective controlled studies.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.217-222
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• 1999

Purpose : To evaluate prognostic factors and survival rates of the patients who received radiation therapy for locally recurrent uterine cervical cancer after curative surgery. Materials and Methods : Between October 1983 and July 1990, fifty three patients who received radiation therapy for locally recurrent cervical cancer after curative surgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, The Catholic University of Korea were analysed retrospectively. Age at diagnosis ranged from 33 to 69 years (median 53 years). Pathological analysis showed that forty five ($84.9\%$) patients had squamous cell carcinoma, seven ($13.2\%$) patients had adenocarcinoma, and one (1.9%) patient had adenosquamous cell carcinoma. The interval between hysterectomy and tumor recurrence ranged from 2 months to 25 years (mean 34.4 months). The recurrent sites were vaginal stump in 41 patients ($77.4\%$) and pelvic side wall in 12 patients ($22.6\%$). Recurrent tumor size was devided into two groups : less than 3 cm in 43 patients ($81.1\%$) and more than 3 cm in 10 patients ($18.9\%$). External beam irradiation of whole pelvis was done first up to 46.8 Gy to 50.4 Gy in 5 weeks to 6 weeks, followed by either external beam boost to the recurrent site in 18 patients ($34\%$) or intracavitary irradiation in 24 patients ($45.3\%$). Total dose of radiation ranged from 46.8 Gy to 111 Gy (median 70.2 Gy). Follow up period ranged from 2 to 153 months with a median of 35 months. Results : Overall response rate was $66\%$ (35/53). Among them, six patients ($17.1\%$) relapsed between 7 months and 116 months after radiation therapy (mean 47.7 months), Therefore overall recurrence rate was $45.3\%$. Overall five-year actuarial survival rate was $78.9\%$ and distant failure rate was $10\%$ (5/50). The significant prognostic factors affecting survival rate were interval between primary surgery and tumor recurrence (p=0.0055), recurrent tumor size (p=0.0039), and initial response to radiation therapy (p=0.0428). Complications were observed in 10 ($20/%$) patients, which included mild to moderate lower gastrointestinal, genitourinary, or skin manifestations. One patient died of pulmonary embolism just after intracavitary irradiation. Conclustion : Radiation therapy is the effective treatment for the patients with locally recurrent cervical cancer after curative surgery. These results suggest that interval between primary surgery and tumor recurrence, recurrent tumor size, and initial response to radiation therapy were significant prognostic factors for recurrent cervical cancer.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.709-719
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• 1996

Background: Surgical resection is the only way to cure non-small cell lung cancer(NSCLC) and the prognosis of NSCLC in patients who undergo a complete resection is largely influenced by the pathologic stage. After surgical resection, recurrences in distant sites is more common than local recurrences. An effective postoperative adjuvant therapy which can prevent recurrences is necessary to improve long tenn survival Although chemotherapy and radiotherapy are still the mainstay in adjuvant therapy, the benefits of such therapies are still controversial. We initiated this retrospective study to evaluate the effects of adjuvant therapies and analyze the prognostic factors for survival after curative resection. Method: From 1990 to 1995, curative resection was perfomled in 282 NSCLC patients with stage I, II, IIIa, Survival analysis of 282 patients was perfonned by Kaplan-Meier method. The prognostic factors, affecting survival of patients were analyzed by Cox regression model. Results: Squamous cell carcinoma was present in 166 patients(59%) ; adenocarcinoma in 86 pmients(30%) ; adenosquamous carcinoma in II parients(3.9%); and large cell undifferentiated carcinoma in 19 patients(7.1%). By TNM staging system, 93 patients were in stage I; 58 patients in stage II ; and 131 patients in stage rna. There were 139 postoperative recurrences which include 28 local and 111 distant failures(20.1% vs 79.9%). The five year survival rate was 50.1% in stage I ; 31.3% in stage II ; and 24.1% in stage IIIa(p <0.0001). The median survival duration was 55 months in stage I ; 27 months in stage II ; and 16 months in stage rna. Among 131 patients with stage rna, the median survival duration was 19 months for 81 patients who received postoperative adjuvant chemotherapy only or cherne-radiotherapy and 14 months for the other 50 patients who received surgery only or surgery with adjuvant radiotherapy(p=0.2982). Among 131 patients with stage IIIa, the median disease free survival duration was 16 months for 21 patients who received postop. adjuvant chemotherapy only and 4 months for 11 patients who received surgery only(p=0.0494). In 131 patients with stage IIIa, 92 cases were in N2 stage. The five year survival rate of the 92 patients with N2 was 25% and their median survival duration was 15 months. The median survival duration in patients with N2 stage was 18 months for those 62 patients who received adjuvant chemotherapy and 14 months for the other 30 patients who did not(p=0.3988). The median survival duration was 16 months for those 66 patients who received irradiation and 14 months for the other 26 patients who did not(p=0.6588). We performed multivariate analysis to identify the factors affecting prognosis after complete surgical resection, using the Cox multiple regression model. Only age(p=0.0093) and the pathologic stage(p<0.0001) were significam prognostic indicators. Conclusion: The age and pathologic stage of the NSCLC parients are the significant prognostic factors in our study. Disease free survival duration was prolonged with statistical significance in patients who received postoperative adjuvant chemotherapy but overall survival duration was not affected according to adjuvant therapy after surgical resection.

• The Journal of Korean Society for Radiation Therapy
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• v.32
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• pp.17-29
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• 2020

Purpose: The purpose of this work was to investigate the dosimetric impact of mixed energy partial arc technique on prostate cancer VMAT. Materials and Methods: This study involved prostate only patients planned with 70Gy in 30 fractions to the planning target volume (PTV). Femoral heads, Bladder and Rectum were considered as oragan at risk (OARs). For this study, mixed energy partial arcs (MEPA) were generated with gantry angle set to 180°~230°, 310°~50° for 6MV arc and 130°~50°, 310°~230° for 15MV arc. Each arc set the avoidance sector which is gantry angle 230°~310°, 50°~130° at first arc and 50°~310° at second arc. After that, two plans were summed and were analyzed the dosimetry parameter of each structure such as Maximum dose, Mean dose, D2%, Homogeneity index (HI) and Conformity Index (CI) for PTV and Maximum dose, Mean dose, V70Gy, V50Gy, V30Gy, and V20Gy for OARs and Monitor Unit (MU) with 6MV 1 ARC, 6MV, 10MV, 15MV 2 ARC plan. Results: In MEPA, the maximum dose, mean dose and D2% were lower than 6MV 1 ARC plan(p<0.0005). However, the average difference of maximum dose was 0.24%, 0.39%, 0.60% (p<0.450, 0.321, 0.139) higher than 6MV, 10MV, 15MV 2 ARC plan, respectively and D2% was 0.42%, 0.49%, 0.59% (p<0.073, 0.087, 0.033) higher than compared plans. The average difference of mean dose was 0.09% lower than 10MV 2 ARC plan, but it is 0.27%, 0.12% (p<0.184, 0.521) higher than 6MV 2 ARC, 15MV 2 ARC plan, respectively. HI was 0.064±0.006 which is the lowest value (p<0.005, 0.357, 0.273, 0.801) among the all plans. For CI, there was no significant differences which were 1.12±0.038 in MEPA, 1.12±0.036, 1.11±0.024, 1.11±0.030, 1.12±0.027 in 6MV 1 ARC, 6MV, 10MV, 15MV 2 ARC, respectively. MEPA produced significantly lower rectum dose. Especially, V70Gy, V50Gy, V30Gy, V20Gy were 3.40, 16.79, 37.86, 48.09 that were lower than other plans. For bladder dose, V30Gy, V20Gy were lower than other plans. However, the mean dose of both femoral head were 9.69±2.93, 9.88±2.5 which were 2.8Gy~3.28Gy higher than other plans. The mean MU of MEPA were 19.53% lower than 6MV 1 ARC, 5.7% lower than 10MV 2 ARC respectively. Conclusion: This study for prostate radiotherapy demonstrated that a choice of MEPA VMAT has the potential to minimize doses to OARs and improve homogeneity to PTV at the expense of a moderate increase in maximum and mean dose to the femoral heads.

• Journal of Life Science
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• v.19 no.5
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• pp.671-675
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• 2009

Prostate cancer has been a critical health problem due to an increase of prostate cancer-related deaths worldwide. Also, a frequent treatment option for prostate cancer is androgen ablation, but this treatment has a limited scope, especially for hormone-refractory cancer. There is an urgent need for the identification of alternative therapeutic strategies for prostate cancer. Previously, over one hundred species of dried-plant methanol extracts were tested for inhibitory effects on proliferation. One of them, Piper longum Linn. was selected based on its potent anti-proliferation effect. The dried root of P. longum Linn. was extracted with 100% methanol for 2-3 days and its extract was fractionated using chloroform. The chloroform layer was then subjected to column chromatography on silica gel, reverse phase-18 (RP-18) and Sephadex LH-20, in turn. Finally, the pure compound was obtained and identified as pipernonaline by NMR spectroscopic and physico-chemical analysis. In this study, anti-proliferation and cell cycle arrest effects of pipernonaline on human prostate cancer PC-3 cells were investigated using the MTT and PI staining, respectively. Our findings suggest that pipernonaline represents a dose-dependent growth inhibition pattern on PC-3 cells and, moreover, its growth inhibition is associated with sub-G1 and G0/G1 cell cycle accumulation in PC-3 cells. Also, these results provide an anticancer candidate for human prostate cancer.