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Biomedical subjects

K H Shin

Publications and source records attributed to K H Shin.

At least 91 records · Page 5Linked to original sources
PubMed1994

Inactivation of the p53 gene by either mutation or HPV infection is extremely frequent in human oral squamous cell carcinoma cell lines.

The state of p53 tumour suppressor and the frequency of high-risk human papillomavirus (HPV) infections were studied in nine human oral cancer cell lines. Three cancer cell lines (SCC-4, Tu-177 and FaDu) had similar amounts of p53 transcripts to normal cells, but contained significantly higher levels of p53 protein than the normal control cells. Sequencing highly conserved open reading frames of the p53 gene of these cancer cells showed point mutations in the SCC-4 and Tu-177 cell lines, a base transition from CCC to TCC occurred at codon 151; and in the line FaDu, a mutation of CGG to CTG occurred at codon 248. The HEp-2 and 1483 cancer lines contained significantly lower levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations, but northern analysis revealed that these cell lines expressed HPV-18 E6/E7 messages. Four cell lines (SCC-9, SCC-15, SCC-25, and Tu-139) expressed negligible amounts of p53 transcripts compared to the normal counterpart and undetectable levels of p53 protein. These cell lines contained mutations in the highly conserved open reading frames of the p53 gene as follows: the SCC-9 had a deletion of 32 base pairs between codons 274 and 285; the line SCC-15 had an insertion of five base pairs between codons 224 and 225; the line SCC-25 had a deletion of two base pairs in codon 209; and the Tu-139 line had a deletion of 46 base pairs between codons 171 and 186.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Electron energy constancy check using a five-chamber detector array.

Two methods are shown here to determine the 50% depth ionization (d50) using buildup materials of different thickness placed on top of a five-chamber detector array. In the first method, two sets of different thickness buildup material are required to perform the check, one set for checking 6 and 9 MeV, while another set is used for 12, 16, and 20 MeV electron beam from a Varian Clinac 2100C. The second method only requires two data points to determine the d50 depth for each energy. The d50 depths determined were compared with the d50 depth obtained using a water phantom with ionization chamber measurements. The method is simple to use especially for departments that use a similar detector to perform quality assurance tests such as output/symmetry/flatness check.

Electrons↗
PubMed1994

Uncertainty in delivered dose resulting from the distribution of source activities in a Selectron LDR afterloader.

The uncertainty in the delivered dose resulting from the distribution of 137Cs source activity in a clinical Selectron LDR unit has been studied. A comparison is made of the dose delivered to a point 'A' in an implant with sources of equal activity to the actual dose delivered in the same implant with source activities randomly chosen from the population in the afterloader.

Cesium Radioisotopes↗
PubMed1994

Combined radiotherapeutic and surgical management of a spinal cord compression by extramedullary hematopoiesis in a patient with hemoglobin E beta-thalassemia.

A 22-year-old male with a history of hemoglobin E beta zero-thalassemia presented with thoracic spinal cord compression due to extramedullary hematopoietic tissue in the epidural space. Following decompressive laminectomy, this epidural mass was irradiated to 20.4 Gy in 12 fractions. The patient made a complete recovery from his neurological symptoms following treatment. Follow-up radiographs showed significant reductions in size of the extradural tumor. Results from this case supported by review of the literature suggest that radiation therapy, with or without decompressive surgery, is an effective therapy in treatment of patients with spinal cord compression due to epidural extramedullary hematopoietic tissue.

Adult↗
PubMed1994

Oncologic outcomes of primary bone sarcomas of the pelvis.

Although many studies have been performed for evaluation of surgical techniques and surgical morbidity in cases of primary pelvic sarcoma, few have addressed the long term oncologic outcomes for these patients. Therefore, the outcome of 41 patients with primary pelvic bone sarcomas were followed for 2-13 years (average, 6 years; median, 5 years). There were 18 chondrosarcomas (15 low grade and 3 high grade tumors), 11 osteosarcomas (1 low grade and 10 high grade tumors), 5 high grade malignant fibrous histiocytomas of bone, 5 Ewing's sarcomas, 1 undifferentiated sarcoma, and 1 low grade angiosarcoma of bone. Fifteen of the 17 patients with low grade tumors survived (88%), whereas only 6 of the 24 patients with high grade tumors survived (25%). Local disease recurred in 1 of the 24 (4%) patients with high grade tumors and in none of the patients with low grade tumors. Reoperations for complications were required in 33% of the patients. A difference could not be demonstrated in the quality of surgical margins or in the surgical morbidity, patient survival, and rate of local recurrence between patients treated with hemipelvectomy (8) and those treated with pelvic resection (32). Patients with low grade pelvic sarcomas have a good prognosis after pelvic resection, but those with high grade sarcomas continue to have a poor prognosis.

Adolescent↗
PubMed1994

Effect of UV-irradiation on cell cycle, viability and the expression of p53, gadd153 and gadd45 genes in normal and HPV-immortalized human oral keratinocytes.

We previously demonstrated neoplastic conversion of HPV-immortalized human oral keratinocytes by exposing cells to chemical carcinogens, but failed to transform normal human oral keratinocytes with same chemical carcinogens in vitro. Though the reason for different responses of normal and HPV-immortalized oral keratinocytes to chemical carcinogens remains speculative, the difference may be due to the capacity of normal cells and incapacity of HPV-immortalized cells for repairing damaged DNA induced by carcinogens. Since (1) the repair of damaged DNA takes place in G1/G2 phases of cell cycle, (2) wild type p53 plays major role in the induction of transient G1 and/or G2 arrests, and (3) the expression of gadd45 and gadd153 is also associated with the cell cycle arrest and DNA damage, we investigated transient cell cycle arrest and the expression of p53, gadd45 and gadd153 in normal human oral keratinocytes, HPV-immortalized oral keratinocytes, and an oral cancer cell line expressing mutant p53 after exposing cells to UV light. Normal cells demonstrated transient G1 arrest after exposure to UV light, but other tested cells did not. While UV-irradiation significantly increased the level of intranuclear wild type p53 protein in normal cells, it did not alter p53 protein levels in HPV-immortalized and oral cancer cells. The level of gadd45 transcripts was enhanced in all tested cells, but normal cells demonstrated higher increase in the level of gadd45 after UV-exposure compared to other tested cells. The level of gadd153 gene transcripts was only increased in normal oral keratinocytes after UV-irradiation. These data indicate that UV-induced transient G1 arrest in normal oral keratinocytes may be associated with both enhanced levels of intranuclear wild type p53 protein and gadd45 and gadd153 transcripts.

Blotting, Northern↗
PubMed1993

The influence of field size and other treatment factors on pulmonary toxicity following hyperfractionated irradiation for inoperable non-small cell lung cancer (NSCLC)--analysis of a Radiation Therapy Oncology Group (RTOG) protocol.

PURPOSE: The risk of pulmonary toxicity, observed in an Radiation Therapy Oncology Group Phase I/II randomized dose escalation trial of hyperfractionated irradiation for nonsmall cell lung cancer, was analyzed with regard to custom vs. hand blocking and compliance to protocol specified treatment field parameters. MATERIALS AND METHODS: There were 832 evaluable cases analyzed. The protocol required field margins 2 cm beyond primary tumor and involved nodes. In 674, the field margins were considered "per protocol" or as having minor protocol variations. In 94, margins exceeded protocol specification ("excessive margin" group). In this group, the area (cm2) of the effective (blocked) field and the portion including lung was measured from simulator films with a computer scanning device. Based on size and location of the primary and nodal disease, "per protocol" fields were constructed and the area (cm2) of lung included beyond these margins was estimated. Patients from both groups who received less than 30 Gy to normal lung were excluded from analysis of pulmonary toxicity. RESULTS: Grade 1 acute lung toxicity was higher (p = .009) in the "excessive margin" group compared to the "per protocol" group, whereas late lung toxicity was not significantly different (p = .94). The risk of Grade 2 or greater acute toxicity increased as area of excess irradiated lung increased. Overall lung toxicity, defined as the greater of either acute or late toxicity, was evaluated by multivariate analysis, in relation to assigned dose, effective treated field area, and type of shielding. Overall maximum lung toxicity (> or = Grade 2) was significantly greater in the "excessive margin" group, when lung treated beyond protocol margins exceeded an area of 35 cm2, than in the "per protocol" group, but only when the effective treated field size was > or = 180 cm2 (68% vs. 37%; p = .02). This effect was independent of assigned total dose or type of shielding. CONCLUSION: For nonsmall cell lung cancer treated with hyperfractionated irradiation, the risk of overall pulmonary toxicity was increased for patients treated with field sizes in excess of protocol specified margins of tumor coverage in comparison to patients treated with protocol specified margins. This effect was seen only when the area of lung treated beyond protocol margins exceeded 35 cm2 and when the overall field size was below 180 cm2.

Carcinoma, Non-Small-Cell Lung↗
PubMed1993

HPV-16, tobacco-specific N-nitrosamine, and N-methyl-N'-nitro-N-nitrosoguanidine in oral carcinogenesis.

We previously immortalized human oral keratinocytes by transfection with recombinant human papillomavirus type 16 (HPV-16) DNA and established two cell lines. These transfected cells were morphologically different from the normal counterpart, contained intact HPV-16 DNA in an integrated form, and expressed numerous viral genes. These cells contained lower levels of wild-type p53 protein and higher levels of c-myc mRNAs compared to normal cells. However, they proliferated only in keratinocyte growth medium containing a low level of calcium and were not tumorigenic in nude mice. A HPV-16-immortalized cell line was exposed to either 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone or N-methyl-N'-nitro-N-nitrosoguanidine. Four chemically transformed cell colonies were isolated. These cells proliferated well in Dulbecco's minimum essential medium containing a physiological level of calcium. They contained, similar to the immortalized counterpart, integrated HPV-16 sequences and lower levels of both wild-type p53 protein and DCC messages compared to normal cells. Among the chemically transformed cells, two colonies obtained from 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone exposure demonstrated an enhanced proliferation capacity in nude mice and transcribed a substantially higher amount of HPV-16 E6/E7, epidermal growth factor receptors, and c-myc genes compared with the immortalized counterpart. These experiments indicate that malignant transformation of oral keratinocytes can be caused by a sequential combined effect of "high risk" HPV and tobacco-related carcinogens.

Base Sequence↗
PubMed1992

Immunoscintigraphy in the detection of tuberculosis with radiolabelled antibody fragment against Mycobacterium bovis bacillus Calmette-Guérin: a preliminary study in a rabbit model.

Immunoscintigraphy with radiolabelled monoclonal antibodies is widely used to detect solid tumours, but only a few trials have been carried out concerning the specific in vivo localization of an inflammatory process. The purpose of this study was to investigate the detectability of tuberculous foci utilizing this method with radiolabelled bacillus Calmette-Guérin (BCG)-specific F(ab')2 in rabbits. All of the tuberculous lesions (n = 8) were clearly visualized on serial scintigraphy for up to 48 h after injection of the antibody. Immunohistochemical and Ziel-Neelson staining of the tuberculous lesions confirmed the presence of the tuberculous antigens and bacilli. It failed to demonstrate any sustained retention of the BCG-specific antibody fragment in the control group with syphilitic orchitis (n = 2). Therefore, the specific in vivo localization of tuberculosis is feasible by immunoscintigraphy.

Animals↗
PubMed1991

Comparison of the Radiation Therapy Oncology Group and American Joint Committee on Cancer staging systems among patients with non-small cell lung cancer receiving hyperfractionated radiation therapy. A report of the Radiation Therapy Oncology Group protocol 83-11.

Since 1973, the Radiation Therapy Oncology Group (RTOG) has staged and stratified patients in non-small cell lung cancer (NSCLC) protocols according to the RTOG staging system. In 1985, the American Joint Committee on Cancer (AJCC) revised its lung cancer staging system, with the principle differences from the RTOG system being the staging of involvement of the chest wall and of contralateral mediastinal and hilar lymph nodes. To determine if the AJCC system discriminated outcome differently than the RTOG system in a nonoperative series, all 850 evaluable patients treated with hyperfractionated radiation therapy (RT) on the RTOG protocol 83-11 were restaged by the AJCC system. There was 67% agreement in patient distribution between the following comparable stages in each system: RTOG Stage II/AJCC Stage II; RTOG Stage III/AJCC Stage IIIA; and RTOG Stage IV/AJCC Stage IIIB. Both systems successfully predicted for survival (P less than 0.001), although the RTOG staging was more discriminating (relative risk ratios, 1.59 versus 1.38). Among the 507 favorable patients (those with less than or equal to 5% weight loss and Karnofsky performance status [KPS] of 70 to 100), the RTOG staging was also more predictive (P = 0.004 versus P = 0.01). When RTOG Stage III (462 patients) was divided into those without contralateral mediastinal or hilar adenopathy (AJCC Stage II/IIIA) and those with (AJCC Stage IIIB), a significant survival (P = 0.0001) was noted with 2-year survival rates of 26% versus 4%, respectively. When AJCC Stage IIIA (348 patients) was divided into the patients without chest wall invasion (RTOG Stage II/III) and those with (RTOG Stage IV), a difference in 2-year survival of 22% versus 10% was observed (P = 0.002). Although both staging systems independently predict for survival, a fusion of both staging systems is the most discriminating of outcome. Future nonoperative studies in locally advanced NSCLC should stratify for contralateral nodal involvement (per AJCC staging) and chest wall invasion (per RTOG staging).

Carcinoma, Non-Small-Cell Lung↗
PubMed1991

The crystal structure of licarin-B, (C20H20O4), a component of the seeds of Myristica fragrans.

The crystal structure of licarin-B, a component of Myristicae Semen was determined by single crystal X-ray diffraction analysis. Crystal of the compound, which was recrystallized from the mixture of hexane and ether, is monoclinic with a = 12.740 (1), b = 7.219(1), c = 9.284(1) A, beta = 94.75(1) degrees, Dx = 1.26, Dm = 1.27 g/cm3, space group P2l, and Z = 2. The structure was solved by direct method and refined by least-squares procedure to the final R value of 0.040 for 1532 independent reflections ¿F > or = 3 sigma (F)¿. The compound is a dimeric phenylpropanoid, and belongs to the neolignan analogues. The molecules are arranged along with the screw axis. The intermolecular contacts appear to be the normal van der Waals' forces.

Benzofurans↗
PubMed1991

N2 (clinical) non-small cell carcinoma of the lung: prospective trials of radiation therapy with total doses 60 Gy by the Radiation Therapy Oncology Group.

Clinical Stage III (N2) non-small cell carcinoma of the lung encompasses a large group of patients, frequently treated with radiation therapy alone, who are now considered to have borderline-resectable tumors. Pilot studies are proceeding which use combinations of resection, radiation therapy, and chemotherapy. To place trials of combination therapy in perspective with contemporary results of radiation therapy alone, recently completed trials of the RTOG were analyzed specifically for clinical Stages T1-3N2. A prospective randomized trial of hyperfractionated radiation therapy (HFX), conducted from 1983 through 1987, compared total doses of 60.0, 64.8, and 69.6 Gy using 1.2 Gy bid with greater than or equal to 4 hr interval. After acute and late effects were considered tolerable, 74.4 Gy and 79.2 Gy arms supplanted the two lowest dose arms. Survival was compared among the five total dose arms, and with 60 Gy in 30 fractions in 6 weeks (standard fractionation-STD) from earlier RTOG studies. Of 516 HFX patients analyzed, 296 (57.3%) with Performance Status (PS) 70-100 and less than 5% weight loss (favorable) had a significantly (p = .001) better survival than those with PS 50-69 or weight loss greater than 5%. Patients with RTOG Stage III (361, 70.0%) experienced better survival (p = .027) than RTOG Stage IV M0. The 69.6 Gy total dose arm was significantly (p = .031) better in favorable RTOG Stage III patients than all other total dose arms: the 1-year survival rate was 58% and the 3-year rate was 20%. The 69.6 Gy HFX results were significantly (p = .002) better than results with STD fractionation in comparable patients from earlier RTOG trials (1-year survival = 30%, 3-year survival = 7%). A prospective, randomized Phase III comparison of STD with 60 Gy versus HFX with 69.6 Gy is underway. These results provide benchmarks for studies of surgical resection combined with chemotherapy and/or radiation therapy until results of prospective comparisons with concurrent controls are available.

Adenocarcinoma↗
PubMed1991

Influence of detector size in photon beam profile measurements.

Correction is necessary to account for the detector size in clinical dosimetry of photon and electron beams. This correction is due to the absorbed dose gradient present in a finite-size detector. Further corrections are necessary when the detector and phantom materials are not the same. These corrections are due to the perturbation in the charged-particle fluence. Generally these corrections are applied to measurements along the central axis of the beam. Cross beam profile measurements, however, are not usually corrected for detector size. The ionization profile is also usually assumed to be equivalent to the absorbed dose profile. We have corrected the ionization chamber size effect by two approaches: extrapolation of measurements to zero detector size and deconvolution of measurements using a simple model for the detector response function. We have measured absorbed dose profiles to water using a small water-equivalent plastic scintillation detector. Film profile measurements were also studied. The ionization profile corrected for detector size and absorbed dose profile were not equal, probably due to loss of charged-particle equilibrium in the beam edges. For ionization chamber measurements, knowledge of the charged-particle spectrum is needed to convert ionization to absorbed dose to water. This is not necessary for relative absorbed dose measurements under charged-particle equilibrium. Film has been shown to be a straightforward and reliable method for cross beam profile measurements.

Film Dosimetry↗
PubMed1991

Biopsies of non-small cell lung cancer: central review in cooperative studies of the Radiation Therapy Oncology Group.

Cooperative trials involving many institutions have long been recognized as a major means of gaining enough experience in a reasonably short period of time to determine the effectiveness of new approaches in cancer therapy. In order to make such multiinstitutional trials meaningful, it is necessary to have uniform and objective diagnostic standards in histopathology. Large cooperative therapeutic trials, such as the Radiation Therapy Oncology Group (RTOG) constructs, must rely on the histopathologic diagnoses of many pathologists from varied institutions or subject them to central review, which is a longer and costlier process. This study is an assay of the need for central review in cooperative studies on non-small cell lung cancer, which includes squamous cell, large cell, adenocarcinomas, and combined squamous cell and adenocarcinomas.

Adenoma↗
PubMed1990

Phosphorus metabolites and the distribution of cell cycle phase of RIF-1 tumors in response to 14 Gy irradiation.

Simultaneous measurements of DNA cell phase cycle distributions and in vivo 31P NMR spectroscopy were performed on 40 RIF-1 murine tumors irradiated with 14 Gy of X-radiation. Diploid and tetraploid tumor populations were observed. The cells blocked in G2/M phase were measured as a function of the ratios of tetraploid cell number in G2/M phase versus total cell population measured. The G2/M population reached a maximum at 32 h post irradiation, dropping to control values by 72 h, while the ratio of inorganic phosphate to beta-nucleotide triphosphate dropped significantly at 32 h and remained significantly lower than control up to 72 h post irradiation. Measurements of PME, PDE, PCr, and pH showed no significant variations at any time point. No significant change in host cell population could be observed. Since the measured G2/M population never increased to more than 3% of the total cell population, the change observed in the 31P NMR spectra were not simply the result of possible differences in NMR profiles of the different cell phase populations but were more likely due to a change in the metabolic characteristics or environment of a majority of the cells.

Animals↗
PubMed1990

Influence of hip prostheses on high energy photon dose distributions.

Radiotherapy treatment of patients having a hip prosthesis is a common problem facing dosimetrists and physicists when the treatment plan requires irradiation of the pelvic area. To quantify the perturbation of these devices, attenuation studies were done with 6 and 18 MV photon beams using various hip prostheses models with varying size and composition. These studies have shown that an attenuation of as much as 50% can be found in a single beam profile under the prosthesis. We have studied the capability of a dose planning system to predict the transmission of these devices as compared with measurements.

Alloys↗