• The Journal of the Korean bone and joint tumor society
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• v.1 no.1
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• pp.38-44
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• 1995

Metastatic bone tumor is the most common bone tumor and 32.5% of all primary malignant tumors are eventually metastasize to bone. Metastatic bone tumor has been more frequently encountered disease in the orthopedic fields due to the greater longevity of life of the patients with primary visceral cancers by major advances in early detection, diagnosis, and surgical/radiotherapeutic/chemotherapeutic treatment of primary and metastatic lesions. Therefore, the epidemiologic data about the incidences and the patterns of bone metastasis is important. We reviewed 417 patients who were diagnosed and treated for metastatic bone tumor at Kosin University Medical Center from 1985 to 1993 to analyse the primary lesion, age and sex distributions, location of bone metastasis, patterns of metastasis according to the primary. The results were as follows : 1. The common origin of bone metastasis were lung(29.5%), stomach(15.3%), breast(11.3%), unknown(7.7%), cervix(5.3%), liver(4.8%) in order of frequency. 2. There were 251 men and 166 women and their mean age was 54.8 years and the peak age incidence was in 6th decades. Most cases(85.3%) were occured beyond 5th decades. 3. The preferred sites of metastatic deposits were spine(64.0%), pelvis(40.5%), rib(38.8%), femur(36.7%), skull(21.1%), humerus(13.9%), scapula(13.0%) in order of frequency. In the spine, thoracic(42.1%), lumbar(39.1%), cervical(13.2%), sacral(5.6%) vertebrae were involved in order of frequency. 4. Multiple bone metastases were more common(73.1%) than single metastasis(26.9%). 5. In the lung cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, pelvis, femur. 6. In the stomach cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, femur, pelvis. 7. In the breast cancer, the peak age incidence was 5th decades, and the preferred sites of bone metastasis were spine, rib, pelvis. 8. In the bone metastasis with unknown primary site, the peak age incidence was 7th decades, the preferred sites of bone metastasis were spine, femur, pelvis, and the common histologic types were adenocarcinoma and squamous cell carcinoma.

• Applied Microscopy
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• v.30 no.1
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• pp.45-59
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• 2000

Cis-platin is a widely used anticancer drug against certain solid tumors such as malignant ovarian tumor, malignant carcinoma of head and neck, bladder cancer and cervical cancer of uterus, and its major mechanism of action is inhibition of DNA synthesis of the tumor cell. To investigate the inhibitory effects of cis-platin on the ciliogensis of the ciliated cells in the mucosa of oviduct, the author pursued the alterations of $\alpha-tubulin$, which is the main constituent of the microtubles in cilia, after cis-platin treatment. To eliminate the possible variations due to ovarian cycle, female Spargue-Dawley rats ($150\sim200gm$ in B.W.) were pretreated with estradiol benzoate (20 mg/kg, once a day, for 4 consecutive days). Animals were administrated with cis-platin (6 mg/kg, i.p.) and sacrificed at 1day, 3days, 5days and 7days after treatment, respectively. Immunohistochemistry for $\alpha-tubulin$ using mouse anti-rat $\alpha-tubulin$ monoclonal antibody as primary antibody was done. Immunogold electronmicroscopy for intracellular distributions of $\alpha-tubulin$ was also performed with same primary antibody and Goat anti- mouse IgM which is preconjugated with gold particles of 15 nm as secondary antibody. The results obtained were as follows; 1. Strong immunoreactivity of $\alpha-tubulin$ was observed in ciliated cells of oviducts at 1, 3 and 5 days after estradiol pretreatment. 2. Weak immunoreactivity of $\alpha-tubulin$ was observed in ciliated cells of oviducts at 1 and 3 days after cis-platin treatment but it was recovered to strong immunoreactivity in 5 days 3. In immunogold electronmicroscopy, density of gold particles for $\alpha-tubulin$ reactions was decreased in apical cytoplasm, but few changes were observed in basal body or cilia at 1 and 3 days after cis-platin treatment. From these above results, it is indicated that synthesis of $\alpha-tubulin$ in ciliated cells of rat oviduct is inhibited by cis-platin treatment.

• Radiation Oncology Journal
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• v.6 no.1
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• pp.63-73
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• 1988

One hundred fifty-four patients with the carcinoma of the uterine cervix were studied retrospectively to assess the result and impact of treatment at Department of Radiation Oncology, Korea University, Hae-Wha Hospital from Feb 1981 through Dec. 1986. Prior to radiotherapy, the patients were evaluated and staged by recommendation of FIGO including physical examination, pelvic examination, cystoscopy, rectosigmoidoscopy, chest X-ray, IVP. Ba enema. Also, an additional pelvic CT scan was obtained for some of the patients. The patients were treated by radiotherapy alone or adjuvant postoperative irradiation; in case of radiation therapy only, whole pelvic irradiation was given with Co-60 teletherapy unit via AP and PA parallel opposing fields or 4-oblique fields, 180 cGy per day, 5 days per week and intracavitary insertion was performed. In satges Ia, Ib, and IIa with small primary lesion, external irradiation was initially given to pelvis up to $2,000\~3,000\;cGy/2frac{1}{2}\;-3frac{1}{2}$ weeks and then intracavitary insertion was performed using Fletcher-Mini-Declos Applicator with cesium-137 cources and followed by external irradiation of $1,000\~2,000\;cGy/1frac{1}{2}\;-2frac{1}{2}$weeks via AP and PA parallel opposing fields with midline shield to spare of bladder and rectum. However, if the primary lesion is large, external irradiation was given without midline shield. More than stages IIb, the patients were treated by external beam irradiation up to 5,400cGy/30f for 6 weeks via 4-oblique portals and at the dose of 5,040cGy/28f the field was cut 5cm from the top margin for spare of small bowel, and followed by intracavitary irradiation, If there was residual tumor an additional dose of $900\~l,200cGy/5\~7f$ was given to parametrium and/or residual tumor area. Total dose of radiation to A and B-point were as follows; A-point; In early stages, Ia, Ib, IIa; $8,000\~9,000$ B-point $5,000\~6,000 cGy$ A-point; In advanced stages IIb, IIIa, IIIb; $9,000\~10,000$ B-point $60,000\~7,000cGy$ The results were obtained and as fellows; 1 The patients distribution according to FIGO staging system were stage Ia 6, Ib 27, IIa 28, IIb 54, IIIa 12, IIIb 18, and stage IVa 9. 2. Value of CT scan were demonstration of cervix tumor mass, parametrial and pelvic side wall tumor spread, pelvic and inguinal lymph nodes metastases, and hydronephrosis. Three dimensional quantitative demonstration of tumor volume is also important in planning radiation therapy. Another advantage of CT scan was detection of recurrent tumor after radiation or surgery. 3. Local control rate of tumor according to the size was $91.3\%$ for less than 5cm in size and $44.6\%$ in tumor over 5cm (p<0.0068). 4. Thirty out of 50 recurrent sites has locoregional failures and 17 cases has distant metastases. And the para-aortic lymph nodes were the most common site for distant metastases. 5. The most common complication was temporal rectal bleeding which was controlled most by conservative management. However, 4 patients required for endoscopic cauterization. 6. The 5-year survival rates showed; stage la and Ib $95\%,\;stage\;IIa\;81\%\;stage\;lIb\;67\%,\;stage\;IIIa\;37.7\%,\;stage\;IIIb\;23\%$ and 3-year survival rate of stage IVa showed $11.6%$, retrospectively.

• 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 Journal of Korean Society for Radiation Therapy
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• v.16 no.1
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• pp.73-77
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• 2004

Purpose of the radio-therapy is maximize the radiation dose to the tumor while minimizing the dose to the critical organ. Carcinoma of the uterine cervix treatment are external irradiation or an interstitial brachtheraphy make use of isotope. Brachytherapy is a method of radiotherapy in advantage to achieve better local control with minimum radiation toxicity in comparison with external irradiation because radiation dose is distributed according to the inverse square low of gamma-ray emitted from the implanted sources. Authors make use of the patients data which 192Ir gives medical treatment intrcavity. Intracavitary radiation of the uterine cervix cancer, critical organ take $20\%$ below than exposure dose of A point in the ICRU report. None the less of the advice, Radiation proctitis and radiation cystitis are frequent and problematic early complications in patients treated with radiation for the uterine cervix cancer. In brachytherapy of uterine cervical cancer using a high dose rate remote afterloading system, it is of prime importance to deliver a accurate dose in each fractionated treatment by minimizing the difference between the pre-treatment planned and post-treatment calculated doses. Use of packing to reduce late complications intracavitary radiation of the uterine cervix cancer. Bladder and rectum changes exposure dose rate by radiotherphy make use of packing.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.7-16
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• 1998

Purpose : To evaluate survival rate and prognostic factors affecting survival of patients with esophageal cancer treated with concurrent chemoradiation. Materials and Methods : Eligibility included biopsy proven invasive carcinoma of the cervical or thoracic esophagus, confined to esophagus and mediastinum with or without regional lymph node and supraclavicular lymph node, and ECOG Performance status $H_0-H_2$. Patients received radiation therapy with 5940cGy over 7 weeks and chemotherapy, consisted of 5-FU(1000 $mg/m^2/day$ in continuous infusion for 5 days, days 1 to 5 and days 29 to 33) and mitomycin C($8mg/m^2$ intravenous bolus at day 1). After concurrent chemoradiation, maintenance chemotherapy was followed with 5-FU(1000 $mg/m^2/day$ in continuous infusion for 5 days at 9th, 13th, and 17th weeks) and cisplatin($80mg/m^2$ intravenous bolus at the first day of each cycle). Results : From November 1989 to November 1995, 44 patients were entered in this study. After treatment, complete response rate and partial response rate were $59\%$ and $41\%$. Overall 1, 2, and 5-year survivals were $59\%$, $38\%$, and $9.6\%$(median 17 months), Prognostic factors affecting survival were response to treatment and T-stage. Among 26 complete responders, there were 6 local recurrences, 3 distant recurrences, 1 local and distant recurrence, and 2 unknown site recurrences Acute and chronic complication rates with grade 3 or more were $20\%$ and $13.0\%$ and there was no treatment-related mortality. Conclusion : Concurrent chemoradiation, compared with historical control groups that treated with radiation alone, improved median survival and did not significantly increase treatment-related complications. Complete responders had longer survival duration than partial responders. Predominant failure pattern was local failure. So, efforts to improve local control should be proposed.

• The Korean Journal of Nuclear Medicine
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• v.34 no.4
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• pp.294-302
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• 2000

Purpose: To investigate the mechanisms related to F-18-FDG uptake by tumors, F-18-FDG accumulation was compared with glucose transporter-1 (Glut-1) expression and hexokinase activity in various human cancer cell lines. Materials and Methods: Human colon cancer (SNU-C2A, SNU-C4, SNU-C5), hepatocellular carcinoma (SNU-387, SNU-423, SNU-449), lung cancer (NCI-H522, NCI-H358, NCI-H1299), uterine cervical cancer (HeLa, HeLa 229, HeLa S3) and brain tumor (A172, Hs 683) cell lines were used. After 24 hr incubation of $5{\times}10^5$ cells, 37 kBq F-18-FDG was added and the uptake by cells at 10 min was measured using a gamma counter. Hexokinase activity was measured by continuous spectrophotometric rate determination. To measure mitochondrial hexokinase activity, mitochondrial fraction was separated by a high speed centrifuge. Immunohistochemical staining of Glut-1 was performed, and graded as 0, 1, 2, or 3 according to expression. Results: There was difference among F-18-FDG uptake, total and mitochondrial hexokinase activity, and Glut-1 expression with different cancer cell lines. The correlations of F-18-FDG with total hexokinase and mitochondrial hexokinase activity were low (r=0.27 and 0.26, respectively). Glut-1 expression showed a good correlation with F-18-FDG uptake (p=0.81, p=0.0015). Previously, we reported no correlation of F-18-FDG uptake with hexokinase activity in colon cancer cell lines. Thus, when colon cancer cells were excluded, F-18-FDG uptake showed higher correlation with total hexokinase and mitochondrial hexokinase activity (r=0.81, p=0.0027 and r=0.81, p=0.0049, respectively). Conclusion: Both Glut-1 expression and hexokinase activity were contributing factors related to F-18-FDG accumulation in human cancer cell lines. The relative contribution of Glut-1 expression and hexokinase activity, however, was different among different cancer cell types.