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Biomedical subjects

K H Shin

Publications and source records attributed to K H Shin.

At least 19 recordsLinked to original sources
PubMed1998

Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG #77-06, a phase III study for T1BN0M0 (A2) and T2N0M0 (B) prostate carcinoma.

PURPOSE: To evaluate survival and time to metastatic disease in patients treated for localized prostatic carcinoma in a Phase III radiotherapy (RT) protocol, Radiation Therapy Oncology Group (RTOG) 77-06. Patients with T18N0M0 (A2) or T2N0M0 (B) disease after lymphangiogram (LAG) or staging laparotomy (SL) were randomized between prophylactic radiation to the pelvic lymph nodes and prostatic bed vs. prostatic bed alone. The outcome of both treatment arms, as well as a comparison of the LAG group, to that of the SL group, are updated. METHODS AND MATERIALS: A total of 449 eligible males were entered into RTOG protocol 7706 between 1978 and 1983. Lymph node staging was mandatory but at the physician's discretion; 117 (26%) patients had SL, while 332 (74%) had LAG. Follow-up was a median of 12 years and a maximum of 16 years. For those randomized to receive prophylactic pelvic lymph nodal irradiation, 45 Gy of megavoltage RT was delivered via multiple portals in 4.5-5 weeks, while all patients received 65 Gy in 6.5-8 weeks to the prostatic bed. RESULTS: There was no significant difference in survival whether treatment was administered to the prostate or prostate and pelvic lymph nodes. The SL group had greater 12-year survival than the LAG group (48% vs. 38%, p = 0.02). Disease-free survival was statistically significant, with 38% for the SL group vs. 26% for the LAG group (p = 0.003). Bone metastasis was less common in the SL group (14%) than the LAG group (27%) (p = 0.003). CONCLUSION: At 12-year median follow-up, there still was no survival difference in those patients treated prophylactically to the pelvic nodes and prostatic bed vs. the prostatic bed alone. Those patients not surgically staged with only LAG for lymph node evaluation were less accurately staged, as reflected by a statistically significant reduced survival and earlier metastases.

Aged↗
PubMed1998

Growth suppression mediated by transfection of wild-type hMLH1 in human cancer cells expressing endogenous truncated hMLH1 protein.

Many genes that are frequently mutated in human cancer are known to be involved in the control of normal cellular proliferation. One of the genes involved in DNA mismatch repair is hMLH1, defective mutations of which are found in some familial and various sporadic cancers. Although the DNA mismatch repair activity of hMLH1 has been identified, other biological functions of hMLH1 have not been well investigated. To investigate the effect of wild-type hMLH1 in cellular proliferation, wild-type hMLH1 cDNA was introduced into human colorectal carcinoma cell line HCT116 and human gastric carcinoma cell line SNU-1, each containing a homozygous non-sense mutation at codon 252 and 226 in hMLH1, repectively. The hMLH1-transfected stable clones showed mRNA and protein expression of transfected hMLH1. Three in vitro cell growth experiments demonstrated that compared with parental and vector-transfected control counterparts, both hMLH1-transfected HCT116 and SNU-1 clones displayed: i) decreased cellular proliferation; ii) a significant decrease in the rate of DNA synthesis and iii) a dramatic reduction of anchorage-independence and the size of colonies in semisolid medium. In addition to DNA repair activity, these results suggest that hMLH1 may play a role in the negative regulation of HCT116 and SNU-1 cell growth.

Adaptor Proteins, Signal Transducing↗
PubMed1997

If you 'watch and wait,' prostate cancer may progress dramatically.

PURPOSE: Observation has been proposed as an option for localized prostate cancer. However, most series reporting on 'watch and wait' include patients treated by TUR or hormones that may affect results. We retrospectively reviewed the natural history of truly untreated prostate cancer and report the outcome for these patients. METHODS AND MATERIALS: From 1976 to 1992, 34 patients of median age 70 years (range 56-88) with biopsy proven localized adenocarcinoma of the prostate refused therapy. All had negative bone scan and none underwent TUR or hormone treatment. No patient was lost to follow-up (median 76 months). Failure patterns and survival were analyzed. RESULTS: At diagnosis 27 patients had palpable nodules (T2), of which 13 were well differentiated and 14 moderately differentiated. Seven had moderately differentiated T3 lesions. Mild prostatitis including nocturia, hesistancy, and urgency were reported in 16 T2 and 6 T3 patients. Within 36 months, local progression requiring therapy occurred in all T3, all T2 moderate and 5 of 13 T2 well-differentiated patients. Systemic progression occurred in 6 of 7 T3, 9 of 14 T2 (mod), and 2 of 13 T2 (well) patients. Overall 59% are alive, 26% succumbed to prostate carcinoma and 15% to other causes. CONCLUSION: Observation results in a high rate of local progression requiring intervention (77%) and excessive systemic disease development (50%) for patients with clinically palpable disease. Perhaps this strategy is viable for earlier stage lesions detected by PSA but it must be tested in a rigorous fashion before accepted.

Adenocarcinoma↗
PubMed1997

Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial.

PURPOSE: The value of adjuvant radiation therapy and staging pelvic lymphadenectomy in patients with low-risk, early-stage endometrial cancer is controversial. The aim of this study was to report the long-term survival, rate of recurrences, and complications in patients with Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion treated with hysterectomy (without formal staging pelvic and periaortic lymph node sampling or lymphadenectomy) and postoperative vaginal brachytherapy. METHODS AND MATERIALS: A total of 303 patients with pathologic Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion and nonmalignant peritoneal cytology, were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative vaginal brachytherapy (30 Gy to point 0.5 cm depth) in a prospective study extending from 1958 to 1994. In addition, 29 additional Stage I, Grade 1-2 patients with <50% myometrial invasion and malignant peritoneal cytology were treated with 1 year of progesterone therapy. Patients were followed for 1.2-32 years (median 8.1 y). RESULTS: Six patients had recurrences and died secondary to disease. There were no vaginal recurrences. The 5-, 10-, 20-, and 30-year disease-free survivals of the 303 patients with nonmalignant peritoneal cytology were 98.9%, 97.8%, 96.7%, and 96.7%, respectively. Patients with malignant peritoneal cytology had a 5- and 10-year disease-free survival of 100%. Significant radiation complications occurred in 2.1% of the patients. CONCLUSION: In patients with low-risk, Stage I endometrial cancer, hysterectomy and adjuvant postoperative vaginal brachytherapy provide excellent long-term survival, eliminate vaginal recurrences, and are not associated with significant complications. The addition of 1 year of progesterone therapy to patients with malignant cytology provides 100% long-term survival. Based on these results, patients with low-risk, Stage I endometrial adenocarcinoma do not need formal staging pelvic and periaortic lymphadenectomy.

Adenocarcinoma↗
PubMed1997

Radiation and chemotherapy improve outcome in oligodendroglioma.

PURPOSE: Oligodendroglioma is a rare central nervous system tumor which may occur in pure or mixed histology. This scarcity results in difficulty in defining optimal management, mainly due to a lack of outcome analysis. Results are further complicated because the reported series include patients treated before megavoltage radiation or computed tomographic (CT) scan development. This makes extrapolation of outcome difficult to apply to modern-era patients. We report results obtained by current treatment and evaluation. METHODS AND MATERIALS: Outcome of all 38 patients (age 5-70 years) pathologically diagnosed between 1975 and 1993 were reviewed. Pure lesions were seen in 14 cases, of which three were anaplastic. The remainder had mixed tumors, of which six contained anaplastic astrocytic elements. Each patient had undergone maximal debulking surgery, but all remained with residual disease on postoperative CT. RESULTS: For nonanaplastic lesions, no local failure was seen in any patient receiving postoperative radiation (60 Gy) and chemotherapy (vincristine, procarbazine, and carmustine). Follow-up ranged from 28 to 240 months (median 125; N = 6). No postoperative therapy or chemotherapy alone resulted in local failure in all nine patients at risk [time to failure (TTF): 2-40 months; median 25]. Radiation alone in doses of 50 Gy at 2 Gy per day resulted in all six patients failing (TTF: 12-52 months; median 36). Achieving 60 Gy at 2 Gy a day allowed five of eight patients to remain disease free (disease-free survival: 24-160 months; median 66), with three failing at 26, 40, and 60 months. All lesions containing anaplastic elements underwent postoperative radiation therapy (60 Gy) and chemotherapy, with five of nine patients alive and well (median disease-free survival: 48 months; range 28-120). CONCLUSION: The combination of radiation and chemotherapy increases local control of oligodendroglioma whether they contain pure, mixed, or anaplastic histology. Radiation alone may offer good local control as long as 60 Gy is delivered. Chemotherapy alone appears to delay TTF and may be useful for pediatric patients.

Adolescent↗
PubMed1996

Oncogenic transformation of HPV-immortalized human oral keratinocytes is associated with the genetic instability of cells.

HPV-immortalized human oral keratinocytes can convert to tumorigenic cells when exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but normal human oral keratinocytes cannot transform with a similar exposure. The different responses of these cells could be due to different genetic stability of cells. In as much as genetic stability is determined by cell cycle control and of repair of damaged DNA, we studied the effect of MNNG exposure upon cell cycle progression, expression of p53, WAF1/CIP1 and gadd45, and the mutation frequency of a shuttle vector pS189 in normal human oral keratinocytes, in HPV-immortalized oral keratinocytes, and in an oral cancer cell line expressing mutant p53. Normal cells demonstrated transient cell cycle arrest after exposure to MNNG, but the other tested cells did not. While MNNG exposure significantly increased the levels of intranuclear wt p53 protein and the expression of WAF1/CIP1 and gadd45 genes in normal cells, it did not alter them in the immortalized and cancer cells. The mutation frequency of pS189 plasmid was significantly lower in normal cells than in the other tested cells. These data indicate that malignant conversion of HPV-immortalized oral keratinocytes may, in part, be associated with the cells' genetic instability. The genetic instability may be due to cells' (1) inability to accumulate intranuclear wt p53 to a threshold level at which p53 upregulates the transcription of WAF1/CIP1 and gadd45, resulting in the loss of cell cycle control and (2) inefficient repair of DNA damage caused by genotoxic agents.

Carcinogens↗
PubMed1996

Radiotherapy of intracranial germinomas.

Between 1980 and 1992, 32 patients with intracranial germinomas were treated with radiation. All patients were confirmed histopathologically prior to treatment. Of the 32 intracranial germinomas reviewed, 14 were located in the suprasellar region, 12 in the basal ganglia and thalamus, four in the pineal, and two in both the pineal and suprasellar regions. Three patients had subarachnoid seeding. Craniospinal irradiation was undertaken for 29 patients. The median dose of 54 Gy was delivered to the tumor bed, 36 Gy to the whole brain and 24 Gy to the spinal axis. Five and 10-year survival rates were 96.9 and 96.9%, respectively. Local control was achieved in all patients except one who died of persistent tumor after 2 months following radiotherapy. No intracranial recurrence or spinal metastasis were found. Tumor site did not relate to the prognosis. One patient developed severe intellectual deterioration, three patients had vertebral growth impairment. The present study confirms the excellent result with radiotherapy alone for patients with germinomas.

Adolescent↗
PubMed1996

A simple backup for a radiosurgery treatment planning system.

To calculate the dose distribution and the number of monitor unit (MU) per arc, all radiosurgery systems utilize some sort of computer. These computers are, of course, subject to equipment malfunction such as problems with the magnetic tape drive, keyboard, mouse, etc. Since most radiosurgery procedures are quite invasive and time consuming, it is important to have a reliable and reasonably accurate backup system for planning the treatment. This paper will show that a simple PC based system, along with a digitizer, may be used as a backup for a commercial, VAX based radiosurgery system. A complete radiosurgery planning procedure was carried out on a head phantom with a target imbedded inside. The treatment planning and verification using the PC based system is also compared with that using the VAX based system.

Computer Systems↗
PubMed1996

Enhancement of radiation effect by Ginkgo biloba extract in C3H mouse fibrosarcoma.

BACKGROUND AND PURPOSE: Ginkgo biloba leaf extract (GBE) is known to increase peripheral blood circulation. The hypothesis that GBE may be able to enhance radiosensitivity of tumor by improving tumor blood flow and thus decreasing hypoxic fraction was tested. MATERIALS AND METHODS: Fibrosarcoma (FSaII) growing in C3H mouse leg muscle was used as a tumor model. GBE was given i.p. 1 h before irradiation with or without priming dose given 1 day earlier. Effect on tumor and normal tissue radiation reaction was investigated. RESULTS: Tumor growth delay by radiation was more elongated after two doses (1-day interval) of GBE than after a single dose. Radiation dose for 3-day tumor growth delay was decreased from 12.45 (10.97-13.93) Gy to 6.06 (3.89-8.22) Gy by two doses of GBE [enhancement ratio = 2.06 (1.32-2.79)]. Hypoxic cell fraction was 10.6% (6.3-18.2%) for control, 7.2% (3.8-14.0%) after a single dose (P = 0.18) and 2.7% (1.5-5.0%) after two doses (P < 0.001). Radiation effect on normal tissue, estimated by acute skin reaction and jejunal crypt assay, was not affected by GBE. CONCLUSION: Ginkgo biloba extract enhances radiation effect on tumor without increasing acute normal tissue radiation damage in this model system probably by increasing tumor blood flow and further investigation for this possible radiosensitizer is needed.

Animals↗
PubMed1996

A well-type ionization chamber geometric correction factor.

To correct for the influence of source configuration on the measured activity of spherical and cylindrical brachytherapy sources, a geometric correction factor was calculated for the Standard Imaging HDR-1000 well-type ionization chamber. A Fortran program modelled each source as a lattice of point sources. Because of the cylindrical symmetry of the well chamber, it could be uniquely modelled by point detectors along the perimeter of the radial plane of the detection volume. Path lengths were calculated and attenuation factors were applied to each source-detector point combination individually. The total dose rate at each detection point was found through a Sievert summation of the point source contributions. For 137Cs sources with identical activities, a correction factor of 0.965 +/- 0.005 was calculated, equal to the ratio of the dose rate of the cylindrical source to that of the sphere. Experimental verification using a Nuclear Associates 67-809 series cylindrical sources and an Amersham spherical 137Cs source yielded a correction factor of 0.958 +/- 0.016.

Brachytherapy↗
PubMed1995

Combined oral carcinogenicity of HPV-16 and benzo(a)pyrene: an in vitro multistep carcinogenesis model.

We previously immortalized normal human oral keratinocytes by transfection with recombinant HPV-16 DNA and subsequently exposed the cells to benzo(a)pyrene for 7 days. The exposure to benzo(a)pyrene modified the immortalized cells: the modified cells (HOK-16B-BaP) proliferated in an ordinary culture medium containing physiological calcium level (1.5 mM), but demonstrated only enhanced proliferation capacity without tumor formation in nude mice and failed to show in vitro anchorage-independency. In this study, we further modified the HOK-16B-BaP cells by subculturing the cells in a medium containing benzo(a)pyrene for 6 months. The cells were further modified with a chronic benzo(a)pyrene exposure and were termed HOK-16B-BaP-T cells (1) demonstrated a malignant phenotype in organotypic 'raft' culture, (2) showed in vitro anchorage-independency, (3) developed tumors in nude mice when injected subcutaneously, (4) contained a significantly higher copy number of intact and integrated HPV-16 DNA; (5) contained higher level of HPV-16 E6/E7 messages and E7 protein, (6) were more resistant to transforming growth factor-beta 1 and (7) secreted higher level of vascular endothelial growth factor with molecular weight of 56 kd than parental HOK-16B-BaP cells. However, the levels of p53 and ras proteins and the levels of p53, c-myc and c-fos transcripts in the HOK-16B-BaP-T cells were not different from those in the HOK-16B-BaP cells. The highly conserved coding regions of the p53, c-Ha-ras1, and c-Ki-ras2 genes of the tumor cells were not mutated. These data indicate that the HPV-immortalized human oral keratinocytes can convert to tumorigenic cells by chronic exposure to benzo(a)pyrene. The tumorigenic conversion seems to be associated with (1) the overexpression of viral oncogenes such as E6 and E7 genes, (2) the higher resistance of cells to transforming growth factor-beta 1 and (3) the high secretion of 56 kd vascular endothelial growth factor from the cells.

Animals↗
PubMed1995

Evaluation of a well-type ionization chamber for calibration of HDL and LDR brachytherapy sources.

The Atomlab 44D well-type ionization chamber is being evaluated for calibration of high dose rate (HDR) Ir-192 and low dose rate (LDR) Cs-137 sources. The chamber has a flat response (sweet spot) of +/- 0.5% along approximately 3.5 cm for an Ir-192 HDR linear source and 3 cm for a Cs-137 LDR spherical source. The short-term stability of the chamber was determined using a cylindrical Cs-137 source positioned in the sweet spot region. The chamber response over a range of 17.4 mCi (644 MBq, Cs-137) and 8.82 Ci (326 GBq, Ir-192) is evaluated. The chamber may be used for calibrating the activities of both HDR Ir-192 and LDR brachytherapy sources.

Brachytherapy↗
PubMed1995

A simple device for prostate and rectal localization in radiation therapy.

A simple device for prostate and rectum localization in radiation therapy may be constructed as follows: first, dental wax is used to make up a shape of the rectal probe. Second, dental stone is used to make a two-piece mold by molding the dental wax probe. Third, using the mold, the rectal probe is made from a mixture of silicone and barium. The final step involves the attachment of the "plug," which is made of aluminum. From the simulation films for the prostate setup, the location of the anterior wall of the rectum, anal sphincter, and anal verge can easily be identified, such that the appropriate regions are shielded accordingly. A CT scan with the probe in the rectum did not give too much artifacts from the barium/silicone mixture. The rectal probe with the plug is useful for localizing the prostate more accurately, compared with using the other rectal localization techniques such as barium injection or some rectal markers.

Aluminum↗
PubMed1995

Application of the "bioeffects" algorithm of a treatment planning system.

In this study, both a four-field box and two-field AP/PA treatment plan are combined with two insertions of Cs-137 in a tandem and ovoids setup, to evaluate the bioeffects program of a treatment planning system. External beam energies studied are 18 and 6 MV. It is shown that there is a slight difference in the 50-70 time dose fractionation (TDF) isolines when comparing 6 MV and 18 MV, for the AP/PA setup. There is practically no difference for TDF isoline values larger than 80 for both energies with either the four-field or the two-field setup. This is because the brachytherapy contributed the majority of the dose to the regions near the applicator and the TDF values reflect the higher dose delivered by the brachytherapy relative to the external beams in that region. For this simple evaluation of the bioeffects program, the combination of the external beam plan and the brachytherapy plan does not give us enhanced information on the effectiveness of the plan.

Algorithms↗
PubMed1995

Evaluation of dose delivery based on a comparison of dosimetry calculations using open beam and wedged beam depth dose data.

The purpose of this study is to evaluate the magnitude of the error in dose delivery caused by the use of open beam depth dose data in dosimetry calculations for wedged photon beams. Isodose plans were calculated for treatments given in a 3-field isocentric prostate or rectal setup using an open AP beam with two lateral wedged beams. The dose distributions were first calculated using open beam depth dose data for all three fields. Next, the open beam data was used only for the AP field and true wedged beam depth dose data was substituted for the two lateral wedged fields. The magnitude of the depth dose variations for wedged vs open beams depends on the nominal beam energy, the wedge angle, and the depth of measurement. Consequently, isodose distributions calculated for wedged fields were found to be different when true wedged beam depth dose data was used instead of open beam data as is commonly done. Monitor unit calculations using a field size specific wedge factor show that dose delivery errors up to 4% can result from the use of open beam depth dose data in wedged beam dose distribution calculations for a 6-MV photon beam. Accurate treatment planning for wedged fields requires the use of wedged beam depth dose data specific to each wedge. Simply using open beam depth dose data in dose calculations for wedged beams will result in dose delivery errors, the magnitude of which depends on the combination of wedge angle, field size, and nominal beam energy.

Evaluation Studies as Topic↗
PubMed1995

The use of customized spreadsheets in radiation therapy.

A number of radiation-therapy-related uses based on a commercially available spreadsheet program have been developed at our facility. The graphics and display capabilities inherent in these spreadsheet programs allow for concise visual results. The spreadsheets are used as an independent check for several types of radiation therapy dose calculations. External beam--a spreadsheet will verify the monitor units (MU) or time required to deliver a prescribed dose to a point on an isodose line as calculated by a commercial treatment planning system. Calibration--spreadsheet programs have been developed to perform the calculations necessary for the output calibration of cobalt and high-energy photon and electron beams according to the TG-21 protocol. The user must indicate which beam, electrometer, chamber, phantom material, temperature, pressure and depth of measurement that apply. Radiosurgery--the MU per arc is calculated based on the following: the average depth per arc as obtained from a commercial radiosurgery program, the collimator size, and the prescription dose. TBI--The patient's width is entered into the spreadsheet program, which then calculates the MU needed to deliver a prescribed dose to the midline.

Humans↗