• Radiation Oncology Journal
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• v.24 no.1
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• pp.51-57
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• 2006

Puroose: We examined whether intratumoral (i.t.) administration of dendritic cells (DCs) into a treated tumor could induce local and systemic antitumor effects in a mouse tumor model. Methods and Materials: C57BL/6 mice were inoculated s.c. in the right and left thighs with MCA-102 fibrosarcoma cells on day 0 and on day 7, respectively. On day 7, the tumors (usually 6 mm in diameter) on the right thigh were heated by immersing the tumor-bearing leg in a circulating water bath at $43^{\circ}C$ for 30 min; thereafter, the immature DCs were i.t administered to the right thigh tumors. This immunization procedure was repeated on days 7, 14 and 21. The tumors in both the right and left thighs were measured every 7 days and the average sizes were determined by applying the following formula, tumor $size=0.5{\times}(length+width)$. Cytotoxicity assay was done to determine tumor-specific cytotoxic T-lymphocyte activity. Results: Hyperthermia induced apoptosis and heat shock proteins (HSPs) in tumor occurred maximally after 6 hr. For the local treated tumor, hyperthermia (HT) alone inhibited tumor growth compared with the untreated tumors (p<0.05), and furthermore, the i.t. administered DCs combined with hyperthermia (HT + DCs) additively inhibited tumor growth compared with HT alone (p<0.05). On the distant untreated tumor, HT alone significantly inhibited tumor growth (p<0.05), and also HT + DCs potently inhibited tumor growth (p<0.001); however, compared with HT alone, the difference was not statistically significant. In addition, HT + DCs induced strong cytotoxicity of the splenocytes against tumor cells compared to DCs or HT alone. Conclusion: HT + DCs induced apoptosis and increased the expression of HSPs, and so this induced a potent local and systemic antitumor response in tumor-bearing mice. This regimen may be beneficial for the treatment of human cancers.

• Radiation Oncology Journal
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• v.23 no.2
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• pp.71-77
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• 2005

Purpose: This retrospective study was conduced to analyze the treatment results and to evaluate the prognostic factors affecting the survival of nasopharyngeal carcinoma patients. Materials and Methods: From 1987 to 2002, we analyzed 43 patients who had nasopharyngeal carcinomas that were histologically confirmed and who had also completed the planned radiation therapy course at Keimyung University Dongsan Medical Center According to the 6th edition of American Joint Committee on Cancer staging system, 12 patients ($27.9\%$) were at Stage 11, 13 ($30.2\%$) were at Stage III and 18 ($41.9\%$) were at Stage IV Histopathologically, there were 15 ($34.9\%$) squamous cell carcinomas, 8 ($18.5\%$) nonkeratinizing carcinomas, 17 ($39.5\%$) undifferentiated carcinomas, and 3 ($7.0\%$) lymphoepitheliomas. Among the total 43 patients, 31 patients ($72.1\%$) were treated with only radiation therapy. Neoadjuvant chemotherapy was peformed on 7 patients ($16.3\%$) and concurrent chemoradiotherapy was performed on S patients ($11.6\%$). Cisplatin and 5-Fluorouracil were administered to 11 patients for 4 cycles, and Cisplatin and Taxotere were administered to 1 patient for 6 cycles. The range of the total radiation dose delivered to the primary tumor was from 61.2 to 84 Gy (median 70.4 Gy), The follow-up period ranged from 2 to 197 months with median follow-up of 84 months. Results: The local control rate at 6 months after radiation therapy was $90.7\%$. The five year overall survival and disease free survival rates were $50.7\%$ and $48.9\%$, respectively. On the multivariate analysis, the age, T-stage ($T_{1-3}\;vs\;T_4$), N-stage and AJCC stage were the statistically significant prognostic factors affecting survival (p<0.05). The patterns of failure were as follows: local failure only in 3 patients ($7.0\%$), local and systemic failure in 1 patient ($2.3\%$), and distant metastasis only in 11 patients ($25.6\%$). Conclusion: The prognostic factors affecting the outcome of nasopharyngeal carcinoma were age, T-stage (7$T_{1-3}\;vs\;T_4$), N-stage and stage. Because systemic metastasis was the main failure pattern noted for nasopharyngeal carcinoma, systemic chemotherapy is needed to decrease the rate of distant metastasis for nasopharyngeal carcinoma. In audition, research for more effective chemotherapeutical regimens and schedules is also needed.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.51-61
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• 1998

Purpose : Treatment of choice for uterine cervix cancer stage IIB is radiotherapy. We analyzed survivals, Prognostic factors, patterns of failure and complications. Materials and Methods : This is a retrospective analysis of 167 patients with stage IIB carcinoma of uterine cervix treated with curative external pelvic and high dose rate intracavitary radiotherapy at the Department of Therapeutic Radiology, Soonchunhyang University Hospital from August 1985 to August 1994. All the patients followed up from 3 to 141 months(mean 60 months) and age of patients ranged from 31 to 78 years at presentation(mean : 55 years). Results : Overall complete response rate was $84\%$. The response rate for squamous cell carcimoma and adenocarcinoma were $86\%$ and $60\%$, respectively. Overall 5-years survival rate and disease free survival rate was 62 and $59\%$, respectively Mass size and treatment response were significant Prognostic factors for survival Pathologic type and parametrial involvement were marginally significants Prognostic factors. Local failure was 43 cases, distant metastasis was 14 cases and local failure plus distant metastasis was 3 cases, and most of local failures occurred within 24 months, distant metastasis within 12 months after treatment Twenty eight($16.8\%$) patients developed late rectal and urinary complications There were tendency to increasing severity and frequency according to increased fractional dose and total(rectal and bladder) dose. Conclusions : Survival rate was significantly related to tumor size and radiotherapy response. Tumor size should be considered in the clinical s1aging. To increased survival and local control, clinical trials such as decreasing duration of radiotherapy or addition of chemotherapy is needed. To detect early recurrence, regular follow up after RT is important. Because total rectal and bladder dose affected late complications. meticulous vaginal packing is needed to optimize dose of normal tissues and to decrease late complications.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.447-454
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• 1998

Purpose : This study evaluated the survival, local control, prognostic factor, and failure pattern of patients with esophageal cancer treated with operation and adjuvant radiation therapy to use as fundermental data of postoperative radiation therapy. Materials and Methods : A retrospective analysis was undertaken of 82 patients who had locally advanced esophageal cancer treated with operation and adjuvant radiation therapy from January 1988 to December 1995. According to AJCC staging, stage IIA were in 26 patients, stage IIB in 4 patients, and stage III in 52 patients. Squamous cell carcinoma were in 77 patients, adenosquamous carcinoma in 3 patients, and adenocarcinoma in 2 patients. The patients received radiation therapy ranging from 41.0 Gy to 64.8 Gy. Five patients received neoadjuvant chemotherapy. Results : Two-year survival and local control rates for all patients were 36.8$\%$ and 30.4$\%$ respectively. And they were 9.3$\%$ and 26.3$\%$ respectively at 5 years. According to stages, 2-year survival rates were 50.2$\%$ in IIA, 0$\%$ in IIB and 23.3$\%$ in III (p=0.004). Two-year local control rates were 49.2 $\%$ in IIA, 66.6$\%$ in IIB and 24.7$\%$ in III (p=0.01). Sixty patients developed recurrence, which were 3 tumor margin, 23 lymph node recurrence, 4 tumor margin and lymph node, 1 tumor margin and distant metastasis, 9 lymph node and distant metastasis, 17 distant metastasis and 3 unknown metastatic site. Prognostic factors affecting survival were smoking (p=0.02), T-staging (p=0.0092), N-staging (p=0.0045). Prognostic factors affecting local control were T-staging (p=0.019), N-staging (p=0.047). Conclusion : In spite of post-operative radiation therapy, predominant failure pattern was local failure. Especially regional lymph node failure was major cause of local failure. So strategy of aggresive adjuvant radiation therapy to regional lymph node area in post operative treatment should be proposed.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.288-297
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• 2004

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.254-264
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• 2004

Purpose: This study was carried out to confirm clinical values and limitations of postoperative radiotherapy for hypopharyngeal carcinoma, to evaluate various prognostic factors which may affect to the treatment results and to use these results as fundamental data for making a new treatment strategy. Methods and Materials:. A retrospective analysis was peformed on 64 previously untreated patients with squamous cell carcinoma of the hypopharynx, seen between 1988 and 1999 at Pusan National University Hospital. Most of patients were treated by laryngopharyngectomy and neck dissection followed by conventional fractionated postoperative radiotherapy on surgical bed and cervical nodal areas. Results: The five-year overall survival rate and cause-specific survival rate were 42.2 percent and 51.6 percent, respectively. Univariate analysis of various clinical and pathologic factors confirmed the overall stage, TN-stage, secondary primary cancers, surgical positive margin, nodal extracapsular extension, total radiation doses as significant prognostic factors of hypopharyngeal carcinomas. But in multivariate analysis, TN-stage, surgical positive margin and extracapsular extesion were only statistically significant. Conclusion: In resectable cases of hypopharyngeal carcinoma, combined surgery and postoperative radio-therapy obtained good treatement results, even though sacrificing the function of larynx and pharynx. But in advanced and unresectable cases, with respect to survivals and qualify of life issues, we were able to confirm some limitations of combined therapy. So we recommend that comparative studies of recent various chemo-radiotherapy methods and advanced radiotherapy techniques with these data should be needed.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.265-270
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• 2004

Purpose: To evaluate the effectiveness of postoperative radiation therapy in cervical cancer patients and define the prognostic factors to affect survival rates. Materials and Methods: Eighty one patients with cervical cancer who were treated with postoperative radiation therapy following surgery at our institution between May 1992 and April 2000 were retrospectivelv analyzed. Forty two patients had stage IB disease, 17 had stage IIA disease, and remaining 22 had stage IIB disease, respectively. Histological examination revealed 76 squamous cell carcinoma and 5 adenocarclnoma. Sixty one patients were noted to have stromal invasion greater than 8 mm and 20 patients were noted to have stromal invasion 7 mm or less. Sixteen patients had parametrial invasion and 65 patients did not. Positive vaginal resection margin was documented in only eight patients and positive lymphovascular invasion was in twelve patients. All of the patients were treated with external beam radiation therapy alone. Majority of the patients were treated with 4 field brick technique to encompass whole pelvis. Total of 5,500 cGy was delivered to the primary surgical tumor bed. Minimum follow up period was four years. Results: Actuarial disease free survival rates for entire group of the patients were 95% and 89% at 2 and 5 years, respectively Five year disease free survival rates for patients with stage IB, IIA, and IIB disease were 97%, 87% and 70%, respectivelv. Local recurrences were documented in 5 patients. Cumulative local failure rate at 3 years was 6% Five year disease free survival rates for patients with stromal invasion greater than 8 mm and 7 mm or less were 88% and 92%, respectively (p>0.05). Five year disease free survival rate for patients with parametrial invasion was significantly lower than those with no invasion (72% vs 92%, p<0.05). Also there was significantly lower survival in patients with positive vaginal resection margin, compared with patients with negative resection margin (64% vs 94%, p<0.05). However, lymphovascular invasion was not a statistically significant prognostic factor Parametrial invasion and positive surgical resection margins were noted to be significant prognostic factors. Conclusions: Postoperative radiation therapy appears to be beneficial in controlling local disease in cervical cancer patients with high pathologic risk factors. Parametrial invasion and positive resection margins were noted to be significant prognostic factors to affect survival and more effective treatment should be investigated in these patients.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.57-63
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• 2010

Purpose: We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). Materials and Methods: From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirtytwo patients (84%) had advanced stage NPC (2002 AJCC Stage III~IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. Results: The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent (${\geq}50%$) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. Conclusion: High Met extent (${\geq}50%$) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.

• Korean Journal of Veterinary Research
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• v.25 no.1
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• pp.7-17
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• 1985

Many investigators have been pursuing various attempts so far to produce hepatitis B surface antigen(HBsAg) vaccines using the techniques such as isolation from plasma of chronic HBsAg carrier, recombinant DNA technique or preparation of synthetic peptides specific for immunogenic determinants. Hepatitis B virus can not grow on any cell lines by the tissue culture technique at the present time. The plasma of chronic HBsAg carrier is expensive and its source is limited. The HBsAg from the recombinant DNA technique gave still very low yield. Another approach, therefore, has been initiated to develop a synthetic hepatitis B virus vaccine. The possible use of several distinct synthetic vaccines in prophylaxis can be facilitated by availability of full synthetic immunogens. Peptides synthesized for potential application as antiviral vaccines have been mostly tested in the form of conjugates with carrier proteins, although the free synthetic peptide can be immunogenic. To understand basic knowledges on the antigenicity and immunogenicity of a synthetic peptide specific for major immunogenic determinant of HBsAg, a nonapeptide, $H_2N^{139}Cys-Thr-Lys-Pro-Thr-Asp-Gly-^{146}Asn-Aba$ COOH, which corresponds to HBsAg amino acid residues 139 to 147, was synthesized by the Merrifield's solid-phase method with a slight modification. The antigenicity and immunogenicity of this specific synthetic peptide were examined comparing with purified plasma-derived natural HBsAg. The results obtained are as follows; 1. The peptide synthesized showed the identical amino acid composition to the theoretical value. The degree of purification and molecular weight were acertained by methods of high performance liquid chromatography and mass spectrometry. 2. Using m-maleimidobenzoyl-N-hydroxysuccinimide ester as a conjugating agent, the synthetic peptide was conjugated to rabbit albumin and ${\gamma}$-globulin, tetanus and diphtheria toxoids, and keyhole limpet hemocyanin. Their conjugation yields were 8.3, 9.5, 15.8, 13.5, and 11.2%, respectively. 3. The natural HBsAg was purified from plasma of chronic HBsAg carrier. By the electron microscopic observation of the purified natural HBsAg preparation, no Dane particles were observed and the preparation showed negative DNA polymerase activity. 4. Antigenicity of the synthetic peptide and the plasma-derived natural HBsAg was determined by competition radioimmunoassay using $^{125}I$-natural HBsAg. Their 50% inhibitions appeared as $90{\mu}g/ml$ and $0.12{\mu}g/ml$ for the synthetic peptide and the natural HBsAg, respectively. This indicates that the former was about 750-fold less antigenic than the latter. 5. Immunogenicity of the synthetic peptide was determined by administering the peptide-carrier conjugates into rabbits with and without Freund's complete adjuvant. Regardless the carrier proteins and adjuvant, positive immune responses to the synthetic peptide were observed. The higher antibody titers, however, were shown in the groups administered with Freund's complete adjuvant. 6. Immunizing dose 50% in mice of the various peptide-carrier conjugates was 5.47, 6.00, 65.16, 31.25 and $13.03{\mu}g/dose$ for rabbit albumin and ${\gamma}$-globulin, tetanus and diphtheria toxoids, and keyhole limpet hemocyanin, respectively, while the natural HBsAg showed $0.65{\mu}g/dose$. 7. It was postulated that homologous proteins prefer to heterologous ones as the carriers.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.603-613
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• 1995

Plasma progesterone($P_4$) assay has been introduced to apply to the differential diagnosis of reproductive disorders and the monitoring of responses of ovarian dysfunction to $PGF_2{\alpha}$ or GnRH treatment in the 204 postpartum and postinsemination subestrus dairy cows. 1. The incidence rate of reproductive disorders in 204 subestrus cows, diagnosed by palpation per rectum and plasma $P_4$ determination using 'Two sample test'(Day 0+Day 10) were as follows; silent heat or error of estrus detection 110(53.9%), persistent corpus luteum 26(12.7%), follicular cyst 16(7.8%), inactive ovary 12(5.9%), luteal cyst 11(5.4%), granulosa cell tumor of ovary 1(0.5%), fetal mummification 1(0.5%), endometritis 15(7.4%) and pyometra 12(5.9%), respectively. 2. After the $PGF_2{\alpha}$ treatment to the 76 cows with silent heat or error of estrus detection, persistent corpus luteum, or luteal cyst, plasma $P_4$ concentrations at day 3 post treatment using 'Two sample test'(Day 0+Day 3) remained low(<1.0ng/ml) in all 76 cows. Therefore all 76 cows responded positively to $PGF_2{\alpha}$ treatment. Seventeen cows with follicular cyst or inactive ovary were treated with GnRH. All 7 cows with follicular cyst and 4 cows with inactive ovary remained high($${\geq_-}1.0ng/ml$$) a plasma $P_4$ concentrations at day 12 post treatment using 'Two sample test'(Day 0+Day 12), but 6 cows with inactive ovary remained low(<1.0ng/ml) a plasma $P_4$ concentrations. Therefore all 7 cows with follicular cyst and 4 cows with inactive ovary responded positively, but 6 cows with inactive ovary responded negatively to GnRH treatment. 3. The mean days from treatment to first service, number of cows conceived on first service(%), mean number of services per conception, mean days from initial treatment to conception, and mean number of cows conceived by 100 days post treatment(%) were 5.0 and 26.2 days, 45(59.2%) and 6(35.3%) cows, 1.5 and 1.7 services, 13.6 and 22.6 days, and 62(81.6%) and 9(52.9%) cows in group of $PGF_2{\alpha}$ and GnRH treatment, respectively. These results indicated that plasma $P_4$ assay was practical as an aid to diagnosing reproductive disorders and to monitoring responses of ovarian dysfunction to $PGF_2{\alpha}$ and GnRH treatment in subestrus cows.