• The Korean journal of internal medicine
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• v.39 no.2
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• pp.318-326
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• 2024

Background/Aims: Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. Methods: This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10-100 ng/mL, 100-500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. Results: This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. Conclusion: High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

• Radiation Oncology Journal
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• v.28 no.3
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• pp.155-165
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• 2010

Purpose: In order to evaluate the positional uncertainty of internal organs during radiation therapy for treatment of liver cancer, we measured differences in inter- and intra-fractional variation of the tumor position and tidal amplitude using 4-dimentional computed radiograph (DCT) images and gated orthogonal setup kilovolt (KV) images taken on every treatment using the on board imaging (OBI) and real time position management (RPM) system. Materials and Methods: Twenty consecutive patients who underwent 3-dimensional (3D) conformal radiation therapy for treatment of liver cancer participated in this study. All patients received a 4DCT simulation with an RT16 scanner and an RPM system. Lipiodol, which was updated near the target volume after transarterial chemoembolization or diaphragm was chosen as a surrogate for the evaluation of the position difference of internal organs. Two reference orthogonal (anterior and lateral) digital reconstructed radiograph (DRR) images were generated using CT image sets of 0% and 50% into the respiratory phases. The maximum tidal amplitude of the surrogate was measured from 3D conformal treatment planning. After setting the patient up with laser markings on the skin, orthogonal gated setup images at 50% into the respiratory phase were acquired at each treatment session with OBI and registered on reference DRR images by setting each beam center. Online inter-fractional variation was determined with the surrogate. After adjusting the patient setup error, orthogonal setup images at 0% and 50% into the respiratory phases were obtained and tidal amplitude of the surrogate was measured. Measured tidal amplitude was compared with data from 4DCT. For evaluation of intra-fractional variation, an orthogonal gated setup image at 50% into the respiratory phase was promptly acquired after treatment and compared with the same image taken just before treatment. In addition, a statistical analysis for the quantitative evaluation was performed. Results: Medians of inter-fractional variation for twenty patients were 0.00 cm (range, -0.50 to 0.90 cm), 0.00 cm (range, -2.40 to 1.60 cm), and 0.00 cm (range, -1.10 to 0.50 cm) in the X (transaxial), Y (superior-inferior), and Z (anterior-posterior) directions, respectively. Significant inter-fractional variations over 0.5 cm were observed in four patients. Min addition, the median tidal amplitude differences between 4DCTs and the gated orthogonal setup images were -0.05 cm (range, -0.83 to 0.60 cm), -0.15 cm (range, -2.58 to 1.18 cm), and -0.02 cm (range, -1.37 to 0.59 cm) in the X, Y, and Z directions, respectively. Large differences of over 1 cm were detected in 3 patients in the Y direction, while differences of more than 0.5 but less than 1 cm were observed in 5 patients in Y and Z directions. Median intra-fractional variation was 0.00 cm (range, -0.30 to 0.40 cm), -0.03 cm (range, -1.14 to 0.50 cm), 0.05 cm (range, -0.30 to 0.50 cm) in the X, Y, and Z directions, respectively. Significant intra-fractional variation of over 1 cm was observed in 2 patients in Y direction. Conclusion: Gated setup images provided a clear image quality for the detection of organ motion without a motion artifact. Significant intra- and inter-fractional variation and tidal amplitude differences between 4DCT and gated setup images were detected in some patients during the radiation treatment period, and therefore, should be considered when setting up the target margin. Monitoring of positional uncertainty and its adaptive feedback system can enhance the accuracy of treatments.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.136-141
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• 2001

Purpose : To evaluate the significance of serum SCC for the monitoring of treatment response and the early detection of distant metastasis during radiotherapy (RT). Materials and Methods : In 13 patients with histologically proven primary squamous cell carcinoma of uterine cervix, serum SCC values were checked in pre-RT point, weekly during RT, and in post-RT point. Results : In 4 of 13 cases, metastasis appeared at the end of external RT, so that intracavitary radiation couldn't be peformed.01 these 4 cases,3 with elevated pre-RT SCC level, who resulted in lung metastasis on chest PA at the end of external RT showed decreased post-RT SCC value despite of metastasis. Of all 10 cases with elevated pre-RT SCC value (including 3 with metastasis at the end of external RT), SCC value was higher than pre-RT value in 7 at 9 Gy and the difference was statistically significant. At 18 Gy, SCC was higher in 4 and lower in 6 than pre-RT value. After 18 Gy, SCC value decreased continuously to the end of RT in all 10 cases. Conclusion : During RT, SCC value increased initially at 9 Gy. To 18 Gy, SCC value decreased to the nearly same with pre-RT value. After 18 Gy, to the end of RT, SCC value decreased continuously and normalized in completely responded cases. In cases with appearance of lung metastasis, SCC value also decreased with the disappearance of main mass of uterine cervix despite metastasis.

• Journal of the Korean Society of Radiology
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• v.9 no.4
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• pp.205-211
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• 2015

At a recent medical imaging technology, the major issue of X-ray diagnosis in breast cancer is the early detection of breast cancer and low patient's exposure dose. As one of studies to acquire a monochromatic X-ray, Technologies using multilayer mirror had been preceded. However, a uniform multilayer mirror that consists of uniform thin-film thickness can acquire a monochromatic X-ray only in the partial area corresponds to angle of incidence of white X-ray, so there are limits for X-ray imaging technology applications. In this study, we designed laterally graded multilayer mirror(below GML) that reflects same monochromatic X-ray over the entire area of thin-film mirror, which have the the thickness of the linear gradient that correspond to angle of incidence of white X-ray. By using ion-beam sputtering system added the mask control system we fabricated a GML which has size of $100{\times}100mm^2$. The GML is designed to achieve the monochromatic X-ray of 17.5kev energy and has thin-film thickness change from 4.62nm to 6.57nm(3.87nm at center). It reflects the monochromatic X-ray with reflectivity of more than 60 percent, FWHM of below 2.6keV and X-ray beam width of about 3mm. The monochromatic X-ray corresponded to 17.5keV using GML would have wide application in development of mammography system with high contrast and low dose.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.3
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• pp.245-253
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• 2000

The development and progression of oral cancer is associated with an accumulation of multiple genetic alterations through the multistep processes. Comparative genomic hybridization(CGH), newly developed cytogenetic and molecular biologic technique, has been widely accepted as a useful method to allow the detection of genetic imbalance in solid tumors and the screening for chromosome sites frequently affected by gains or losses in DNA copy number. The authors examined 19 primary oral squamous cell carcinomas using CGH to identify altered chromosome regions that might contain novel oncogenes and tumor suppressor genes. Interrelationship between these genetic aberrations detected and major oncogenes and tumor suppressor genes previously recognized in carcinogenesis of oral cancers was studied. 1. Changes in DNA copy number were detected in 14 of 19 oral cancers (78.9%, mean: 5.58, range: $3{\sim}13$). High level amplification was present in 4 cases at 9p23, $12p21.1{\sim}q13.1$, 3q and $8q24{\sim}24.3$. Fourteen cases(78.9%, mean: 3.00, range: $1{\sim}8$) showed gains of DNA copy number and 12 cases(70.5%, mean: 2.58, range: $1{\sim}9$) revealed losses of DNA copy number. 2. The most common gains were detected on 3q(52.6%), 5p(21.0%), 8q(21.0%), 9p(21.0%), and 11q(21.0%). The losses of DNA copy number were frequently occurred at 9p(36.8%), 17q(36.8%), 13q(26.3%), 4p(21.0%) and 9p(21.0%). 3. The minimal common regions of gains were repeatedly observed at $3q24{\sim}26.7$, $3q27{\sim}29$, $1q22{\sim}31$, $5p12{\sim}13.3$, $8q23{\sim}24$, and 11q13.1-13.3. The minimal common regions of losses were detected at $9q11{\sim}21.3$, 17p31, $13q22{\sim}34$, and 14p16. 4. In comparison of CGH results with tumor stages, the lower stage group showed more frequent gain at 3q, 5q, 9p, and 14q, whereas gains at 1q($1q22{\sim}31$) and 11q($11q13.1{\sim}13.3$) were mainly detected in higher stage group. The loss at $13q22{\sim}34$ was exclusively detected in higher stage. The results indicate that the most frequent genetic alterations in the development of oral cancers were gains at $3q24{\sim}26.3$, $1q22{\sim}31$, and $5p12{\sim}13.3$ and losses at $9q11{\sim}21.3$, 17p31, and 13q. It is suggested that genetic alterations manifested as gains at $3q24{\sim}26.3$, $3q27{\sim}29$, $5p12{\sim}13.3$ and 5p are associated with the early progression of oral cancer. Gains at $1q22{\sim}31$ and $11q13.1{\sim}13.3$ and loss at 13q22-34 could be involved in the late progression of oral cancers.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.2
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• pp.164-173
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• 2000

The p16 protein is a cyclin dependent kinase inhibitor that inhibits cell cycle progression from $G_1$ phase to S phase in cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers, and alterations of p16 gene function by DNA methylation have been noticed in various kinds of cancer tissues and cell-lines. There have been a large body of literature has accumulated indicating that abnormal patterns of DNA methylation (both hypomethylation and hypermethylation) occur in a wide variety of human neoplasma and that these aberrations of DNA methylation may play an important epigenetic role in the development and progression of neoplasia. DNA methylation is a part of the inheritable epigenetic system that influences expression or silencing of genes necessary for normal differentiation and proliferation. Gene activity may be silenced by methylation of up steream regulatory regions. Reactivation is associated with demethylation. Although evidence or a high incidence of p16 alterations in a variety of cell lines and primary tumors has been reported, that has been contested by other investigators. The precise mechanisms by which abnormal methylation might contribute to carcinogenesis are still not fully elucidated, but conceivably could involve the modulation of oncogene and other important regulatory gene expression, in addition to creating areas of genetic instability, thus predisposing to mutational events causing neoplasia. There have been many variable results of studies of head and neck squamous cell carcinoma(HNSCC). This investigation was studied on 13 primary HNSCC for p16 gene status by protein expression in immunohistochemistry, and DNA genetic/epigenetic analyzed to determine the incidence, the mechanisms, and the potential biological significance of its Inactivation. As methylation detection method of p16 gene, the methylation specific PCR(MSP) is sensitive and specific for methylation of any block of CpG sites in a CpG islands using bisulfite-modified DNA. The genomic DNA is modified by treatment with sodium bisulfate, which converts all unmethylated cytosines to uracil(thymidine). The primers designed for MSP were chosen for regions containing frequent cytosines (to distinguish unmodified from modified DNA), and CpG pairs near the 5' end of the primers (to provide maximal discrimination in the PCR between methylated and unmethylated DNA). The two strands of DNA are no longer complementary after bisulfite treatment, primers can be designed for either modified strand. In this study, 13 paraffin embedded block tissues were used, so the fragment of DNA to be amplified was intentionally small, to allow the assessment of methylation pattern in a limited region and to facilitate the application of this technique to samlples. In this 13 primary HNSCC tissues, there was no methylation of p16 promoter gene (detected by MSP and automatic sequencing). The p16 protein-specific immunohistochemical staining was performed on 13 paraffin embedded primary HNSCC tissue samples. Twelve cases among the 13 showed altered expression of p16 proteins (negative expression). In this study, The author suggested that low expression of p16 protein may play an important role in human HNSCC, and this study suggested that many kinds of genetic mechanisms including DNA methylation may play the role in carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7825-7829
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• 2015

Background: Egypt has the highest prevalence of HCV infection in the world (~14.7%). Around 10-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. The incidence of HCC is expected to grow in the next two decades, largely due to HCV related cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. No simple reliable non-invasive marker has been available till now. B2M, a non-glycosylated polypeptide composed of 99 amino acids, is one of the components of HLA class I molecules on the surfaces of all nucleated cells. It has been reported that the level of serum B2M is elevated in patients with chronic hepatitis C and HCV-related HCC when compared to HCV-negative patients or healthy donors. Determining the clinical utility of serum B2M as a marker for disease progression in Egyptian patients with HCV related chronic hepatitis, cirrhosis and hepatocellular carcinoma was the aim of the present study. Materials and Methods: In this analytical cross sectional study 92 participants were included in 4 equal groups: Group (1) non cirrhotic chronic HCV; Group (2) HCV related liver cirrhosis; Group (3) HCC on top of HCV,; and Group (4) healthy controls. History taking, clinical examination, routine labs and abdominal ultrasound were conducted for all patients, PCR and Metavir scores for group (1) patients, and triphasic CT abdomen and AFP for Group (3) patients. B2M levels were measured in serum with a fully-automated IMX system. Results: The mean serum B2M level of Group (1) was $4.25{\pm}1.48{\mu}g/ml$., Group (2) was $7.48{\pm}3.04$, Group (3) was $6.62{\pm}2.49$ and Group (4) was $1.62{\pm}0.63$. Serum B2M levels were significantly higher in diseased than control group (p<0.01) being significantly higher in cirrhosis ($7.48{\pm}3.04$) and HCC groups ($6.62{\pm}2.49$) than the HCV group ($4.25{\pm}1.48$) (p<0.01). There was a significant correlation between B2M Level and ALK, total and direct bilirubin and INR (p<0.05), and a significant inverse correlation between B2M level and albumin, total proteins, HB andWBCS values (p<0.05). There was no significant correlation between B2M level and viral load or Metavir score, largest tumour size or AFP (p>0.05). The best B2M cut-off for HCV diagnosis was 2.6 with a sensitivity of 100%, a specificity of 92%, a positive predictive value (PPV) of 97% and a negative predictive value (NPV) of 100%. The best B2M cut-off for HCC diagnosis was 4.55 which yielded sensitivity, specificity, positive predictive value, negative predictive values of 74%, 62%, 39.5, 87.8% respectively (p-value <0.01) while best cut-off for cirrhosis was 4.9, with sensitivity 74 % and specificity 74%.The sensitivity for HCC diagnosis increased upon B2M and AFP combined estimation to 91%, specificity to 79%, NPV to 95% and accuracy to 83%. Conclusions: Serum B2M level is elevated in HCV related chronic liver diseases and may be used as a marker for HCV disease progression towards cirrhosis and carcinoma.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.46-53
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• 2005

Purpose: Bisphosphonates (BPs) are the analogues of endogenous pyrophosphates: they have been used in the treatment of skeletal diseases such as Paget's disease, osteoporosis, and tumorinducing ostelysis, and are used in treatment of osteolytic metastasis of breast cancer recently. They are also used as one of the therapeutic agents for metastasis of prostatic cancer of which metastasis makes the mixed nature of osteolysis and ostegenesis. Although the action mechanism of BPs are well known for diseases with excessive osteoclastic bone resorption, the direct effect of BPs has not been known yet. This study was intended to see the tumor suppression capability of Zoledronic acid(ZOL) using nude mouse with osteosarcoma. Materials and Methods: MG-63 and HOS osteosarcoma cell lines were used and the transforemed MG-63-GFP and HOS-GFP cells, which were made for detection under fluorescent light, were subcutaneously injected to make osteosarcoma. The five 6-week male mice were used for the experiment at each group. After the injection, mice were cultivated until tumor pieces grow up to $3{\times}3{\times}3$ $mm^3$ and ZOL of 120 ug/kg was subcutaneously injected twice a week. Sizes of tumor were measured twice a week and photographed under fluorescent light. Results: In in vivo test with HOS osteosarcoma cell lines, mean size of tumors was 2,520 $mm^3$ in control group and was 131 $mm^3$ in ZOL group, which showed 94% of reduction comparing with the control ; with MG-63 osteosarcoma cell lines, mean size of tumors was 2,866 $mm^3$ in control group and was 209 $mm^3$ in test group with 72% of reduction (p<0.05). Conclusion: In in vivo tests with nude mice, we suggest that ZOL has direct effect on osteosarcoma cells and it would be used as one of the therapeutic agents for osteosarcoma, especially to ZOL-sensitive osteosarcoma cells.

• Journal of Radiation Protection and Research
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• v.25 no.4
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• pp.223-232
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• 2000

Comparative study was performed for the assessment of DNA damage and Chromosomal aberration in human lymphocyte exposed to low dose radiation using fluorescence in situ hybridization(FISH) and single cell gel electrophoresis(SCGE). Chromosomal aberrations in human lymphocytes exposed to radiation at doses of 5, 10, 30 and 50cGy were analysed with whole chromosome-specific probes by human chromosome 1, 2 and 4 according to PAINT system. FISH with chromosome-specific probe has been used to be a valid and rapid method fer detection of chromosome rearrangements induced by low dose radiation. The frequencies of stable translocation per cell equivalents were 0.0116, 0.0375, 0.040f, 0.0727 and 0.0814 for 0, 5, 10, 30 and 50cGy, respectively, and those of dicentric were 0.00, 0.0125, 0.174, 0.0291 and 0.0407 respectively. Radiation induced DNA damage in human lymphocyte in a dose-dependent manner at low doses from 5cGy to 50cGy, which were analysed by single tell gel electrophoresis(SCGE). From above results, FISH seemed to be useful for radiation biodosimetry by which the frequencies of stable aberrations in human lymphocyte can be observed more easily than by conventional method and SCGE also seemed to be sensitive method f9r detecting DNA damage by low dose radiation exposure, so that those methods will improve our technique to perform meaningful biodosimetry for radiation at low doses.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.194-200
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• 2009

Purpose: This aim of this study was to evaluate changes in gastric volume and organ position as a result of delayed gastric emptying after a subtotal gastrectomy performed as part of the treatment of stomach cancer. Materials and Methods: The medical records of 32 patients who underwent concurrent chemoradiotherapy after a subtotal gastrectomy from March 2005 to December 2008 were reviewed. Of these, 5 patients that had more than 50 cc of residual gastric food detected at computed tomography (CT) simulation, were retrospectively enrolled in this study. Gastric volume and organ location was measured from CT images obtained before radiotherapy, twice weekly. In addition, authors evaluated the change of radiation dose distribution to planning the target volume and normal organ in a constant radiation therapy plan regardless of gastric volume variation. Results: A variation in the gastric volume was observed during the radiotherapy period (64.2~340.8 cc; mean, 188.2 cc). According to the change in gastric volume, the location of the left kidney was shifted up to 0.7 - 2.2 cm (mean, 1.2 cm) in the z-axis. Under-dose to planning target volume (V43, 79.5${\pm}$10.4%) and over-dose to left kidney (V20, 34.1${\pm}$12.1%; Mean dose, 23.5${\pm}$8.3 Gy) was expected, given that gastric volume change due to delayed gastric emptying wasn't taken into account. Conclusion: This study has shown that a great change in gastric volume and left kidney location may occur during the radiation therapy period following a subtotal gastrectomy, as a result of delayed gastric emptying. Detection of patients who experienced delayed gastric emptying and the application of gastric volume variation to radiation therapy planning will be very important.