• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.525-532
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• 1999

The parathyroid hormone related protein (PTHrP) is the most common causative peptide of humoral hypercalcemia of malignancy. In contrast, the serum level of parathyroid hormone (PTH) is low to undetectable in the majority of patients with malignancy associated hypercalcemia. Few cases exist in which the production and secretion of PTH by malignant nonparathyroid tumors have been authenticated. To our knowledge, there is very rare case in which a nonparathyroid tumor expressed simultaneously both the PTH and PTHrP. We report a case of squamous cell carcinoma of the lung with hypercalcemia which presented with simultaneous elevation of serum PTH and PTHrP. Severe hypercalcemia (serum calcium, 7.5 mEq/L) was found in a 65-year-old man who had a squamous cell carcinoma of the lung without any bony metastasis and detectable parathyroid abnormalities on isotope scintigraphy. The serum level of intact parathyroid hormone (PTH) con centration was markedly elevated as measured in two site radioimmunoreactive PTH assays (intact PTH 150 pg/mL ; normal 9~55). The serum level of a PTHrP was also increased as measured in C-terminal region specific radioimmunoassay (PTHrP 99.1 pmol/L; normal 13.8~55.3). There are no evidences of coincidental primary hyperparathyroidism in parathyroid MIBI scan and other imaging studies including neck ultrasonography and computed tomography. These results suggest that simultaneous elevation of serum PTH and PTHrP in this patient can be caused by production of both PTHrP and PTH in other nonparathyroid lesions such as squamous cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.55 no.4
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• pp.378-387
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• 2003

Background : Promoter methylation of tumor suppressor genes is one of the key epigenetic changes in many human cancers. The aim of this study was to evaluate the promoter methylation status of the Death-associated protein(DAP) kinase gene, which played an important role in lung cancer, in the serum DNA of primary lung cancer patients. Methods : This study investigated the aberrant methylation of DAP kinase in the serum of 65 primary lung cancer patients by methylation-specific PCR (MSP). Results : Methylation in the serum was detected in 29 of 65(44.6%) for DAP kinase. There was no statistical association between methylation of DAP kinase and age, smoking history, histologic type, or stage. Methylation of DAP kinase was found more frequently in men (p=0.044). Conclusions : This study suggests that the aberrant methylation of the DAP kinase promoter is readily detectable in the serum DNA of lung cancer patients using MSP analysis.

• Tuberculosis and Respiratory Diseases
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• v.55 no.4
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• pp.388-394
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• 2003

Background : Monoclonal antibodies directed against well-known epitopes on cytokeratin (CK) 8, 18 and 19 (Monototal) have been used in the development of a new diagnostic tool for lung cancer. In the mid-1990s, CK 19 fragments (Cyfra 21-1) became popular and widely used for such diagnosis. This is the first study specifically designed to compare these two markers. Method : The serum levels of CK 8, 18 and 19 were measured using two-site monoclonal/polyclonal immunoradiometric assay kit in 57 healthy adults and 289 patients who were admitted to Seoul National University Hospital from May to September, 2002. The lung cancer group comprised 129 primary lung cancer patients; 116 with non-small cell lung cancer(NSCLC) and 13 with small cell lung cancer (SCLC). The control group comprised 160 non-malignant pulmonary lung disease patients and 57 healthy adults. A total of 166 twin Monototal and Cyfra 21-1 serum assays were obtained; 76 with lung cancer, 70 with non-malignant pulmonary lung disease and 20 healthy adults. Results : The mean serum value of Monototal was $412.47{\pm}455.45U/L$ in NSCLC, $237.08{\pm}145.15U/L$ in SCLC, $126.54{\pm}95.72U/L$ in non-malignant pulmonary lung disease, and $63.68{\pm}31.66U/L$ in healthy adults. The serum values of the lung cancer groups were significantly higher than those of the control group (p<0.01). Using a cut off value of 188U/L, sensitivity and specificity was 66.4% and 81.9% in NSCLC, and 43.8% and 81.9% in SCLC, respectively. The serum levels of CK 8, 18 and 19 were higher in advanced NSCLC than in early stage disease. Conclusion : The serum levels of CK 8, 18 and 19 may be useful in the diagnosis of NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.347-355
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• 2008

Background: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. Methods: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-${\alpha}$ with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. Results: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-${\alpha}$ induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. Conclusion: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.5
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• pp.375-395
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• 2006

Purpose: Lingual nerve (LN) damage may be caused by either tumor resection or injury such as wisdom tooth extraction, Although autologous nerve graft is sometimes used to repair the damaged nerve, it has the disadvantage of necessity of another operation for nerve harvesting. Moreover, the results of nerve grafting is not satisfactory. The nerve growth factor (NGF) is well-known to play a critical role in peripheral nerve regeneration and its local delivery to the injured nerve has been continuously tried to enhance nerve regeneration. However, its application has limitations like repeated administration due to short half life of 30 minutes and an in vivo delivery model must allow for direct and local delivery. The aim of this study was to construct a well-functioning $rhNGF-{\beta}$ adenovirus for the ultimate development of improved method to promote peripheral nerve regeneration with enhanced and extended secretion of hNGF from the injured nerve by injecting $rhNGF-{\beta}$ gene directly into crush-injured LN in rat model. Materials and Methods: $hNGF-{\beta}$ gene was prepared from fetal brain cDNA library and cloned into E1/E3 deleted adenoviral vector which contains green fluorescence protein (GFP) gene as a reporter. After large scale production and purification of $rhNGF-{\beta}$ adenovirus, transfection efficiency and its expression at various cells (primary cultured Schwann cells, HEK293 cells, Schwann cell lines, NIH3T3 and CRH cells) were evaluated by fluorescent microscopy, RT-PCR, ELISA, immunocytochemistry. Furthermore, the function of rhNGF-beta, which was secreted from various cells infected with $rhNGF-{\beta}$ adenovirus, was evaluated using neuritogenesis of PC-12 cells. For in vivo evaluation of efficacy of $rhNGF-{\beta}$ adenovirus, the LNs of 8-week old rats were exposed and crush-injured with a small hemostat for 10 seconds. After the injury, $rhNGF-{\beta}$ adenovirus($2{\mu}l,\;1.5{\times}10^{11}pfu$) or saline was administered into the crushed site in the experimental (n=24) and the control group (n=24), respectively. Sham operation of another group of rats (n=9) was performed without administration of either saline or adenovirus. The taste recovery and the change of fungiform papilla were studied at 1, 2, 3 and 4 weeks. Each of the 6 animals was tested with different solutions (0.1M NaCl, 0.1M sucrose, 0.01M QHCl, or 0.01M HCl) by two-bottle test paradigm and the number of papilla was counted using SEM picture of tongue dorsum. LN was explored at the same interval as taste study and evaluated electro-physiologically (peak voltage and nerve conduction velocity) and histomorphometrically (axon count, myelin thickness). Results: The recombinant adenovirus vector carrying $rhNGF-{\beta}$ was constructed and confirmed by restriction endonuclease analysis and DNA sequence analysis. GFP expression was observed in 90% of $rhNGF-{\beta}$ adenovirus infected cells compared with uninfected cells. Total mRNA isolated from $rhNGF-{\beta}$ adenovirus infected cells showed strong RT-PCR band, however uninfected or LacZ recombinant adenovirus infected cells did not. NGF quantification by ELISA showed a maximal release of $18865.4{\pm}310.9pg/ml$ NGF at the 4th day and stably continued till 14 days by $rhNGF-{\beta}$ adenovirus infected Schwann cells. PC-12 cells exposed to media with $rhNGF-{\beta}$ adenovirus infected Schwann cell revealed at the same level of neurite-extension as the commercial NGF did. $rhNGF-{\beta}$ adenovirus injected experimental groups in comparison to the control group exhibited different taste preference ratio. Salty, sweet and sour taste preference ratio were significantly different after 2 weeks from the beginning of the experiment, which were similar to the sham group, but not to the control group.

• KSBB Journal
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• v.24 no.4
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• pp.403-409
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• 2009

H2AX, a crucial component of chromatin, is implicated in DNA repair, cell cycle check point and tumor suppression. The aim of this study was to identify direct binding partners of H2AX to regulate cellular responses to above mechanisms. Literature reviews and bioinformatical tools were attempted intensively to find binding partners of H2AX, which resulted in identifying two potential proteins, breast cancer-1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1). Although it has been reported in vivo that BRCA1 co-localizes with H2AX at the site of DNA damage, their biochemical mechanism for H2AX were however only known that the complex monoubiquitinates histone monomers, including unphosphorylated H2AX in vitro. Therefore, it is important to know whether the complex directly interacts with H2AX, and also which regions of these are specifically mediated for the interaction. Using in vitro GST pull-down assay, we present here that BRCA1 and BARD1 directly bind to H2AX. Moreover, through combinational approaches of domain analysis, fragment clonings and in vitro binding assay, we revealed molecular details of the BRCA1-H2AX and BARD1-H2AX complex. These data provide the potential evidence that each of the BRCA1 nuclear localization signal (NLS) and BARD1 BRCA1 C-terminal (BRCT) repeat domain is the novel mediator of H2AX recognition.

• Journal of Yeungnam Medical Science
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• v.19 no.2
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• pp.107-115
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• 2002

Purpose: Ga-67 scintigraphy has been used for the evaluation of tumors, especially lymphoma. Recently, Tl-201 and Tc-99m MIBI were also used to tumor imaging. Tl-201 and Tc-99m MIBI had better physiologic characteristics than Ga-67, so we studied 32 biopsy proven lymphoma patients (male 24, female 8, mean age 46 years) with Ga-67, Tl-201 or Tc-99m MIBI and compared the scan findings. Materials and Methods: Twenty-three of 32 patients were injected 74-111 MBq (2-3 mCi) of Tl-201, before chemotherapy and imaged with dual-headed SPECT (Prism 2000, Picker, USA) at 30 minutes after injection. Delayed images were obtained after 3 hr in 8 patients. Twenty seven of 32 patients were injected 740 MBq (20 mCi) of Tc-99m MIBI and imaged at 30 minutes after injection. 111-185 MBq (3-5 mCi) of Ga-67 was injected in 12 patients and imaged at 48 and 72 hours after injection. Twenty eight patients were diagnosed as non-Hodgkin's lymphoma and others were Hodgkin's lymphoma. Results: Twenty patients were positive on Tl-201 scan and 3 patients showed negative findings. One of these 3 patients, Tc-99m MIBI and Ga-67 scan were positive. Twenty two patients were positive on Tc-99m MIBI scan and 5 patients showed negative findings. One of these 5 patients, Tl-201 was positive and 2 were positive on Ga-67 scan. Ten of 12 patients showed positive findings on Ga-67 scan. The sensitivity of these agents were 83.3%, 87.0% and 81.5% for Ga-67, Tl-201 and Tc-99m MIBI, respectively. The sensitivity was highest in Tl-201 scan, but there were no significant differences among three tests. In this study, there was no significant difference of uptake ratios between early and delayed images of Tl-201. Conclusion: Scintigraphy with Tl-201 and Tc-99m MIBI in lymphoma patients have similar sensitivity with Ga-67.

• Progress in Medical Physics
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• v.3 no.2
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• pp.1-12
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• 1992

For intraoperative radiation therapy using electron beams, a cone system to deliver a large dose to the tumor during surgical operation and to save the surrounding normal tissue should be developed and dosimetry for the cone system is necessary to find proper X-ray collimator setting as well as to get useful data for clinical use. We developed a docking type of a cone system consisting of two parts made of aluminum: holder and cone. The cones which range from 4cm to 9cm with 1cm step at 100cm SSD of photon beam are 28cm long circular tubular cylinders. The system has two 26cm long holders: one for the cones larger than or equal to 7cm diamter and another for the smaller ones than 7cm. On the side of the holder is an aperture for insertion of a lamp and mirror to observe treatment field. Depth dose curve. dose profile and output factor at dept of dose maximum. and dose distribution in water for each cone size were measured with a p-type silicone detector controlled by a linear scanner for several extra opening of X-ray collimators. For a combination of electron energy and cone size, the opening of the X-ray collimator was caused to the surface dose, depths of dose maximum and 80%, dose profile and output factor. The variation of the output factor was the most remarkable. The output factors of 9MeV electron, as an example, range from 0.637 to 1.549. The opening of X-ray collimators would cause the quantity of scattered electrons coming to the IORT cone system. which in turn would change the dose distribution as well as the output factor. Dosimetry for an IORT cone system is inevitable to minimize uncertainty in the clinical use.

• Progress in Medical Physics
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• v.23 no.2
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• pp.81-90
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• 2012

The effect of setup uncertainties on CTV dose and the correlation between setup uncertainties and setup margin were evaluated by Monte Carlo based numerical simulation. Patient specific information of IMRT treatment plan for rectal cancer designed on the VARIAN Eclipse planning system was utilized for the Monte Carlo simulation program including the planned dose distribution and tumor volume information of a rectal cancer patient. The simulation program was developed for the purpose of the study on Linux environment using open source packages, GNU C++ and ROOT data analysis framework. All misalignments of patient setup were assumed to follow the central limit theorem. Thus systematic and random errors were generated according to the gaussian statistics with a given standard deviation as simulation input parameter. After the setup error simulations, the change of dose in CTV volume was analyzed with the simulation result. In order to verify the conventional margin recipe, the correlation between setup error and setup margin was compared with the margin formula developed on three dimensional conformal radiation therapy. The simulation was performed total 2,000 times for each simulation input of systematic and random errors independently. The size of standard deviation for generating patient setup errors was changed from 1 mm to 10 mm with 1 mm step. In case for the systematic error the minimum dose on CTV $D_{min}^{stat{\cdot}}$ was decreased from 100.4 to 72.50% and the mean dose $\bar{D}_{syst{\cdot}}$ was decreased from 100.45% to 97.88%. However the standard deviation of dose distribution in CTV volume was increased from 0.02% to 3.33%. The effect of random error gave the same result of a reduction of mean and minimum dose to CTV volume. It was found that the minimum dose on CTV volume $D_{min}^{rand{\cdot}}$ was reduced from 100.45% to 94.80% and the mean dose to CTV $\bar{D}_{rand{\cdot}}$ was decreased from 100.46% to 97.87%. Like systematic error, the standard deviation of CTV dose ${\Delta}D_{rand}$ was increased from 0.01% to 0.63%. After calculating a size of margin for each systematic and random error the "population ratio" was introduced and applied to verify margin recipe. It was found that the conventional margin formula satisfy margin object on IMRT treatment for rectal cancer. It is considered that the developed Monte-carlo based simulation program might be useful to study for patient setup error and dose coverage in CTV volume due to variations of margin size and setup error.

• Progress in Medical Physics
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• v.25 no.4
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• pp.218-224
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• 2014

The small field dosimetry is very important in modern radiotherapy because it has been frequently used to treat the tumor with high dose hypo-fractionated radiotherapy or high dose single fraction stereotactic radiosurgery (SRS) with small size target. But, the dosimetry of a small field (< $3{\times}3cm^2$) has been great challenges in radiotherapy. Small field dosimetry is difficult because of (a) a lack of lateral electronic equilibrium, (b) steep dose gradients, and (c) partial blocking of the source. The objectives of this study were to measure and verify with the various detectors the output factors in a small field (<3 cm) for the 6 MV photon beams. Output factors were measured using the CC13, CC01, EDGE detector, thermoluminescence dosimeters (TLDs), and Gafchromic EBT2 films at the sizes of field such as $0.5{\times}0.5$, $1{\times}1$, $2{\times}2$, $3{\times}3$, $5{\times}5$, and $10{\times}10cm^2$. The differences in the output factors with the various detectors increased with decreasing field size. Our study demonstrates that the dosimetry for a small photon beam (< $3{\times}3cm^2$) should use CC01 or EDGE detectors with a small active volume. And also, Output factors with the EDGE detectors in a small field (< $3{\times}3cm^2$) coincided well with the Gafchromic EBT2 films.