• Radiation Oncology Journal
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• v.14 no.1
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• pp.9-15
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• 1996

Purpose: The traditional approach with surgery and/or radiotherapy(RT) for advanced head and neck cancer Provides anticipated cure rates of $10-65\%$ depending on stages and sites. Recently, combined modality with chemotherapy have been extensively investigated in attempts to improve survival and local control. We retrospectively analysed our experience of 31 patients with advanced head and neck cancer. Materials and Methods : November 1983 to October 1994. 31 Patients with Stage III and IV squamous cell head and neck cancer were treated with RT. Sixteen patients were treated with RT alone, and IS patients were treated with combined RT plus chemotherapy. All patients were treated with 4-MV LINAC and radiation dose ranged from 5000 cGy to 7760 cGy (median 7010 cGy). In combined group, 7 patients were treated with cisplatin plus 5-FU 2 patients were treated with methotrexate plus leucovorin plus 5-FU plus cisplatin or carboplatin, and 6 patients were treated with cisplatin as a radiosensitizer. Results : Median follow up period was 16 months (range 4-134 months). The major responses (CR+PR) were noted in 10 patient ($66.6\%$) of the RT alone group and 14 patient ($93.3\%$) of the chemoradiation group. There was no statistical difference in CR rate between the two groups The overall survival rates at 5 years were $23.4\%$ in the radiation alone group, $23.5\%$ in the chemoradiation group Disease-free survival rates at 3 years were $44.5\%$ in the radiation alone group, $40\%$ in the chemoradiation group. There was no statistical differences in overall survival rates and disease-free survival rates between the two groups. Local recurrences occurred in $71.5\%$ of the radiation alone group, $72.7\%$ of the chemoradiation group and distant metastasis occurred in $14.4\%$ of radiation alone group, $9.1\%$ of the chemoradiation group. The frequencies of complications were comparable in both groups except hematologic toxicity Conclusion : Total response rates in the combined chemotherapy and radiotherapy was relatively higher than radiotherapy alone. But our result failed to show any survival benefit of the combined chemotherapy and radiotherapy. The accrual of large number of patients and long term follow-un may be necessary to confirm the present result of combined chemotherapy and radiotherapy.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.17-24
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• 2004

Purpose: To evaluate the treatment outcomes after postmastectomy radiotherapy (PMRT) and chemotherapy in patients with breast cancer. Materials and Methods: The PMRT were retrospectively analyzed in 83 patients with stage II-III female breast cancer treated between 1989 and 1995. The median age was 46 years (range, 23-77): Seventy-seven patients had modified radical mastectomies, 5 radical mastectomies and 1 simple mastectomy. Three patients ($4\%$) had pathologically negative axillae, and the remaining 80 ($96\%$) had positive axillae. Eleven, 23, 44 and 5 patients had pathological stages IIA, IIB, IIIA, and IIIB, retrospectively. Eighty ($96\%$) patients were treated with hockey-stick fields. The median dose of PMRT was 50.4 ey, in 1.8 Gy fractions. Adjuvant systemic chemotherapy was given to 74 patients ($89\%$). CMF-based or doxorubicin-containing regimens were given to 54 patients ($55\%$). The median follow-up time was 82 months (range, 8-171) after the mastectomy. Results: The 5 and 10-year overall survival rates for all patients were 65 and $49\%$, respectively. The univariate and multivariate analyses of the factors affecting the overall survival revealed the stage to be the most significant prognostic factor (p=0.002), followed by the combination of chemotherapy. Thirteen patients $16\%$ developed a LRF, at an interval of 4-84 months after radiotherapy, with a median of 20 months. The only significant prognostic factor affecting LRF was the combination of chemotherapy, in both the univariate and multivariate analyses. With respect to the sequence of chemoradiation, the sequence had no saatistical significance (p=0.90). According to the time interval from mastectomy to the onset of radiotherapy, the LRFR of the patients group treated by RT within or after 6 month postmastectomy 6 months were 14 vs. $27\%$ respectively (p=0.24). One third of the pa41en1s (26/83) developed distant metastasis, in 2-92 months, after radiotherapy, with a median of 21 months. The most commonly involved site was bone in 13 cases. The pathological staging was the only significant prognostic factor in both the univariate and multivariate analyses that affected distant failure. Radiological finding of radiation pneumonitis on a simple chest x-ray was shown in $20\%$ (17/83), with a time interval ranging from 2 to 7 months post-radiotherapy, with a median of 3 months. The stable lung fibrosis settled in 11 patients ($65\%$). Conclusion: It was concluded through this analysis that the combination of PMRT with in chemotherapy resulted in better overall survival and local control than PMRT alone in patients needing PMRT.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.221-227
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• 2002

Purpose : To evaluate the role of postoperative chemoradiotherapy in locally advanced rectal cancer, we retrospectively analyzed the treatment results of patients treated by curative surgical resection and postoperative chemoradiotherapy. Materials and Methods : From April 1989 through December 1998, 119 patients were treated with curative surgery and postoperative chemoradiotherapy for rectal carcinoma in Gyeongsang National University Hospital. Patient age ranged from 32 to 73 years, with a median age of 56 years. Low anterior resection was peformed in 59 patients, and abdominoperineal resection in 60. Forty-three patients were AJCC stage II and 76 were stage III. Radiation was delivered with 6 MV X rays using either AP-PA two fields, AP-PA both lateral four fields, or PA both lateral three fields. Total radiation dose ranged from 40 Gy to 56 Gy. In 73 patients, bolus infusions of 5-FU $(400\;mg/m^2)$ were given during the first and fourth weeks of radiotherapy. After completion of radiotherapy, an additional four to six cycles of 5-FU were given. Oral 5-FU (Furtulone) was given for nine months in 46 patients. Results : Forty $(33.7\%)$ of the 119 patients showed treatment failure. Local failure occurred in 16 $(13.5\%)$ patients, 1 $(2.3\%)$ of 43 stage II patients and 15 $(19.7\%)$ of 76 stage III patients. Distant failure occurred in 31 $(26.1\%)$ patients, among whom 5 $(11.6\%)$ were stage II and 26 $(34.2\%)$ were stage III. Five-year actuarial survival was $56.2\%$ overall, $71.1\%$ in stage II patients and $49.1\%$ in stage III patients (p=0.0008). Five-year disease free survival was $53.3\%$ overall, $68.1\%$ in stage II and $45.8\%$ in stage III (p=0.0006). Multivariate analysis showed that T stage and N stage were significant prognostic factors for five year survival, and that T stage, N stage, and preoperative CEA value were significant prognostic factors for five year disease free survival. Bowel complication occurred in 22 patients, and was treated surgically in 15 $(12.6\%)$, and conservatively in 7 $(5.9\%)$. Conclusion : Postoperative chemoradiotherapy was confirmed to be an effective modality for local control of rectal cancer, but the distant failure rate remained high. More effective modalities should be investigated to lower the distant failure rate.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.301-317
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• 2005

The number of patients with tongue carcinoma is increasing rapidly among young individuals in many parts of the world. Oral carcinoma progresses from hyperplastic lesion through dysplasia to invasive carcinoma and the concept of "field cancerization" with molecular alteration has been suggested for oral cavity carcinogenesis. Significant improvement in treatment and prognosis will depend on more detailed understanding of the multi-step process leading to cancer development. To induce tongue carcinoma in rat by 4-NQO, each drinking water was made to 10 ppm, 25 ppm, 50 ppm and control (only D.W. without 4-NQO). Specimens were classified into 4 groups such as control, I (mild & moderate dysplasia), II (severe dysplasia and carcinoma in situ), III (carcinoma). The mRNA expressions of Bcl-2 family were evaluated by RT-PCR technique. For anti-apoptotic Bcl-2 family, mRNA expression of Bcl-w was down-regulated in all stages of tongue carcinogenesis model. However, mRNA expression of Bcl-2 was up-regulated. For pro-apoptotic Bcl-2 family, all members were down-regulated in all stages of tongue carcinogenesis model except for Bad mRNA in group III. In terms of BH3 only protein, mRNA expressions of Bok and Mcl-1 were down regulated in all stages of specimen, but Bmf in group II and BBC3 in group III were up-regulated. Our current findings demonstrated the involvements of mRNA expression of Bcl-2 family in multi-step tongue carcinogensis. This highlights the necessity for continued efforts to discover suitable biomakers (Bcl-2 family) for early diagnosis of the disease, and to understand its pathogenesis as a first step in improving methods of treatment. The discovery of these potential biomarkers and molecular targets for cancer diagnostics and therapeutics has the potential to significantly change the clinical approach and outcome of the disease.

• Development and Reproduction
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• v.15 no.2
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• pp.179-185
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• 2011

Some phytoestrogens in soy and red wine, for example, might have beneficiary rather than adverse effects. In particular, dietary soy intake seems to be highly correlated with protection of breast cancer, osteoporosis and cardiovascular disorders. However, questions persist on the potential adverse effects of the main soy constituent genistein (GS) on female reproductive physiology. Previously we found that prepubertal exposure to GS could activate the reproductive system of immature female rats leading to precocious puberty onset, and intracerebroventricularly (ICV) injected GS could directly activate hypothalamic kisspeptin-GnRH neuronal circuits in adult female rats. The present study was performed to examine the hypothalamus-specific GS effects in prepubertal female rats and which subtype of estrogen receptor is mediated in this GS effect. Prepubertal female rats (PND 30) were anaesthetized, treated with single dose of GS (3.4 ${\mu}g$/animal), and sacrificed at 2 hrs post-injection. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). ICV infusion of GS significantly lowered the transcriptional activities of mTOR (1:$0.361{\pm}0.058$ AU, p<0.001) but increased that of GAD67 (1:$1.285{\pm}0.099$ AU, p<0.05), which are known to act as an upstream modulator of kisspeptin and GnRH neuronal activities in the hypothalamus, respectively. GS administration enhanced significantly the mRNA levels of KiSS-1(1:$1.458{\pm}0.078$ AU, p<0.001), and exerted no effect on the mRNA level of kisspeptin receptor GPR-54 (1:$1.29{\pm}0.08$ AU). GnRH gene expression was significantly decreased in GS-treated group compared to control group (1:$0.379{\pm}0.196$ AU, p<0.05). There was no difference in the mRNA level of $ER{\alpha}$ in the GS-treated group compare to control group (1:$1.180{\pm}0.390$ AU, Fig. 3A). However, icv infusion of GS significantly increased the transcriptional activities of $ER{\beta}$ (1:$4.209{\pm}0.796$ AU, p<0.01, Fig. 3B). Taken together, the present study indicated that the acute exposure to GS could directly alter the hypothalamic GnRH modulating system in prepubertal female rats. Our study strongly suggested the involvement of $ER{\beta}$ pathway in GS's hypothalamus-specific action, and this idea is consistent with the GS's well-known $ER{\beta}$-mediated protective action in breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.217-223
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• 2013

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the outcomes for patients are still poor. It is important to determine the original type of synchronous multinodular HCC for preoperative assessment and the choice of treatment therapy as well as for the prediction of prognosis after treatment. Aims: To analyze clinicopathologic characteristics and prognoses in patients with multicentric occurrence (MO) and intrahepatic metastasis (IM) of synchronous multinodular hepatocellular carcinoma (HCC). Methods: The study group comprised 42 multinodular HCC patients with a total of 112 nodules. The control group comprised 20 HCC patients with 16 single nodular HCC cases and 4 HCC cases with a portal vein tumor emboli. The mitochondrial DNA (mtDNA) D-loop region was sequenced, and the patients of the study group were categorized as MO or IM based on the sequence variations. Univariate and multivariate analyses were used to determine the important clinicopathologic characteristics in the two groups. Results: In the study group, 20 cases were categorized as MO, and 22 as IM, whereas all 20 cases in the control group were characterized as IM. Several factors significantly differed between the IM and MO patients, including hepatitis B e antigen (HBeAg), cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and the histological grade of the primary nodule. Multivariate analysis further demonstrated that cirrhosis and portal vein and/or microvascular tumor thrombus were independent factors differentiating between IM and MO patients. The tumor-free survival time of the MO subjects was significantly longer than that of the IM subjects ($25.7{\pm}4.8$ months vs. $8.9{\pm}3.1$ months, p=0.017). Similarly, the overall survival time of the MO subjects was longer ($31.6{\pm}5.3$ months vs. $15.4{\pm}3.4$ months, p=0.024). The multivariate analysis further demonstrated that the original type (p=0.035) and Child-Pugh grade (p<0.001) were independent predictors of tumor-free survival time. Cirrhosis (p=0.011), original type (p=0.034) and Child-Pugh grade (p<0.001) were independent predictors of overall survival time. Conclusions: HBeAg, cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and histological grade of the primary nodule are important factors for differentiating IM and MO. MO HCC patients might have a favorable outcome compared with IM patients.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.7 no.1
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• pp.39-60
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• 2001

Fuzhengfangaitang is a prescript for inhibiting recurrence and metastasis of cancer. We had examined the anti-metatstastic effect of Fuzhengfangaitang. Furthermore, we performed the following experiments with ingredients of Fuzhengfangaitang. The purpose of this thesis is to study what ingredients of Fuzhengfangaitang have more valuable anti-cancer effects. And the results are listed below: 1. Cell Viability assay At the dose of 400$\mu$g/ml, most ingredients of Fuzhengfangaitang depressed viability of ECV-304. And especially, Scutellaria barbata D. DON$50{\mu}g/ml$ : 53.118%, $100{\mu}g/ml$: 49.092%, $200{\mu}g/ml$ : 43.765%, $400{\mu}g/ml$ : 12.747%), Polygonum bistorta L.($50{\mu}g/ml$ : 45.554%, $100{\mu}g/ml$ : 45.554%, $200{\mu}g/ml$ : 0.0%, $400{\mu}g/ml$ : 0.0%) and Psoralea corylifolia L.($50{\mu}g/ml$ : 86.591%, $100{\mu}g/ml$ : 81.307%, $200{\mu}g/ml$ : 24.801%, $400{\mu}g/ml$ : 3.111%) highly depressed cell viability more than the other ingredients. (${\alpha}$<0.05) 2. Cell Proliferation assay Proliferation assay with ingredients of Fuzhengfangaitang on ECV-304 showed that Crataegus pinnatifuda BGE ($50{\mu}g/ml$: 63.276%, $100{\mu}g/ml$ : 64.092%, $200{\mu}g/ml$ : 68.966% $400{\mu}g/ml$ : 38.517%, ED50=$296.974{\mu}g/ml$), Polygonum bistorta L.($50{\mu}g/ml$ : 83.981%, $100{\mu}g/ml$ : 86.997%, $200{\mu}g/ml$ : 58.780%, $400{\mu}g/ml$ : 26.408%), ED50=$266.725{\mu}g/ml$) and Psoralea corylifolia L.($50{\mu}g/ml$ : 103.037%, $100{\mu}g/ml$ : 82.529%, $200{\mu}g/ml$ : 2.829%, $400{\mu}g/ml$ : 0.998%), ED50=$177.369{\mu}g/ml$) depressed cell proliferation more than the other ingredients. 3. Tube Formation assay Compared with the control group, most ingredients of Fuzhengfangaitang did not remarkably inhibited the Tube Formation assay of ECV-304 at the dose of $100{\mu}g/ml$. But, Polygonum bistorta L. highly inhibited the tube formation of ECV -304 at the lower dose of $50{\mu}g/ml$. 4. Rat Aortic Ring assay In comparison with the control group, Scutellaria barbata D. DON., root of Polygonum bistorta L. and Psoralea corylifolia L. restricted the angiogenesis of the rat aortic ring at the dose of $100{\mu}g/ml$. And the other ingredients of Fuzhengfangaitang did not restricted the angiogenesis of the rat aortic ring at that dose. Especially, Polygonum bistorta L. highly inhibited the angiogenesis of the rat aortic ring at the lower dose of $50{\mu}g/ml$. From our research, the anti-angiogenic effects of the ingredients of Fuzhengfangaitang was proven. Moreover, it will be helpful for designing more effective prescription for anti angiogenesis.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.259-265
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• 1993

Between January 1985 and July 1992, 52 patients with locally advanced nasopharyngeal carcinoma were studied retrospectively for the effectiveness of sequential chemotherapy and radiation therapy. The male to female ratio was 3.3:1 with a median age of 41 years. Forty patients had squamous cell carcinoma and the remaining 12 had undifferentiated carcinoma. Seven patients had stage III disease and the remainder had stage IV disease at time of presentation. All patients were treated two courses of chemotherapy followed by radiation therapy. Chemotherapy consisted of either CVB (cisplatin, vincristine and bleomycin) or CF (cisplatin and 5-FU). Total radiation dose to the primary site ranged from 6000 cGy to 7500 cGy. Neck nodes were given booster treatment to maximum of 7000 cGy, depending on the extent of disease. Local control, overall survival and disease-free survival rates were analyzed. The complete response (CR) rate to chemotherapy was $15\%$ and the partial response (PR) rate was $46\%,$ for overall major response rate of $61\%.$ The CR rate was $87\%$ after radiation therapy. Median follow-up time was 51 months. The overall survival and disease-free survival rates at 36 months were $54\%\;and\;49\%,$ respectively. Median time to relapse was 15 months. The patterns of initial relapse in CR patients was as follows: locoregional failure only, 12 patients; distant metastasis only,11: both,2. Cox's multivariate regression model revealed that nodal status was the single most important independant prognostic factor influencing disease-free survival (p=0.001). Comparision of these results with other published reports with radiation therapy alone showed that a high rate of initial response to chemotherapy did not translate into local control or survival. At present time radiation therapy alone remains the standard treatment for locoregional cancer of the nasopharyngeal cancer. More controlled clinical trials must be completed before acceptance of chemotherapy as a part of treatment of advanced nasopharyngeal carcinoma.

• Toxicological Research
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• v.8 no.2
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• pp.343-357
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• 1992

Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.112-117
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• 1993

Background Radioiodine ($^{131}I$), a major component of nuclear fallout and a valuable therapeutic agent for thyrotoxicosis and thyroid cancer, has been regarded as a mutagen or a carcinogen without any convincing evidence. To evaluate the genotoxicity of radioiodine ($^{131}I$) we performed a micronuclei test in mice bone marrow. Materials and methods : Mice (ICR strain, $25{\sim}30 g$) were divided to 4 groups: control, group 1 (0.17 mCi/kg, usual therapeutic dose for thyrotoxicosis), group 2 (1.67 mCi/kg, usual therapeutic dose for thyroid cancer), and group 3 (16.67 mCi/kg, usual accumulated dose causing bone marrow suppression). $^{131}I$ was administered intraperitoneally. Ten mice of each group were sacrificed at days 1 and 3. Bone marrow were smeared and stained with May-Grunwald Giemsa method. One thou-sand polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were counted under the light microscope, and the number of micronucleated PCEs were recorded. Results : The frequency of micronuclei in PCE (and NCE in parenthesis) in the control group was $0.25{\pm}0.07$ ($0.23{\pm}0.07$)% in day 1 and $0.24{\pm}0.07$ ($0.21{\pm}0.07$)% in day 3. Those in group 1 was $0.27{\pm}0.1$ ($0.23{\pm}0.09$)% in day 1 and $0.28{\pm}0.07$ ($0.25{\pm}0.06$)% in day 3. Micronuclei was noted in $0.29{\pm}0.08$ ($0.26{\pm}0.09$)% in day 1 and $0.31{\pm}0.05$ ($0.29{\pm}0.06$)% in day 3 in group 2, and in $0.32{\pm}0.06$ ($0.25{\pm}0.09$)% in day 1 and $0.33{\pm}0.08$ ($0.3{\pm}0.06$)% in day 3 in group 3. There was no difference in the frequency of micronuclei between each groups (p> 0.05). Conclusion : Radioiodine ($^{131}I$) did not cause any genotoxicity in mice bone marrow even at the large dose (16.67 mCi/kg).