Even the overall incidence is decreasing and the proportion of early gastric cancer is increasing from the national mass screening program, still gastric cancer is the major issue in Korea. Multimodality approach and the development of novel therapeutic agents enabled us to improve the survival rate of gastric cancer. However, the proper treatment strategy for the subgroups of patients is necessary, which is now categorized based on the clinicopathologic parameters. We need more in-depth information regarding the molecular biology of gastric cancer, and the development of novel targeted biological agents and the biomarkers for the future. Currently, the recent chemotherapeutic agents showed the improved response in advanced gastric cancer. Hence, the basic concept of adjuvant chemotherapy, palliative chemotherapy, neoadjuvant treatment with or without incorporation of radiotherapy become settle down with more evidences from several phase III trials. Especially, after understanding the difference between Asia and Western countries including biology, ethnic difference, operation technology, and the treatment approaches, the qualified, well-designed multinational clinical trials are on-going. Based on the current results, here, I describe the current status of gastric cancer treatment strategy.
Asia ; Biological Agents ; Biomarkers ; Biology ; Chemotherapy, Adjuvant ; Humans ; Incidence ; Korea ; Mass Screening ; Molecular Biology ; Neoadjuvant Therapy ; Stomach Neoplasms ; Survival Rate

Based on recently developed biotechnology, many new drugs have been developed for improving patient treatment outcomes. To develop novel drugs, proper clinical trials are essential. As clinical trials involve humans in research, the protection of participants is important not only for the participants' safety but also for future patients. Ethics in a clinical trial is not the same as in clinical practice with enough evidence. Hence, the whole procedure of a clinical trial should be well organized, scientifically and ethically planned, and monitored properly by an Institutional Review Board (IRB). Here the importance of ethics in clinical trials, related issues, and the monitoring system will be discussed.
Biotechnology ; Ethics Committees, Research ; Humans

PURPOSE: Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are associated with increased angiogenesis, growth, and metastasis in solid tumors. But, until today, the importance of theses factors on leukemia, especially childhood acute lymphocytic leukemia (ALL) has received limited attention. Therefore, this study examined the bone marrow plasma VEGF and bFGF levels in ALL patients and normal controls. PATIENTS AND METHODS: Bone marrow plasmas at diagnosis from 33 ALL patients (median age 5.9 years; range 1.8-13.9 years) were used for analysis. The bone marrow levels of bFGF and VEGF were determined by enzyme-linked immunosorbent assay (R & D Systems) and compared with the bone marrow levels of 7 healthy control subjects (median age 11.98 years; 6 months -13.6 years). RESULTS: Average VEGF was higher in relapse ALL (N=7, 216.6 +/- 79.9pg/mL) compared to standard (N=9, 36.8 +/- 12.1pg/mL) (p=0.013) or high risk ALL (N=17, 80.0 +/- 12.2pg/mL) (p=0.023). bFGF levels were also significantly higher in relapse than standard-, or high-risk ALL patients (relapse ALL; 48.6 +/- 15.4pg/mL, standard risk ALL; 18.9 +/- 5.5pg/mL, high risk ALL; 19.0 +/- 3.5pg/mL, normal control; 18.6 +/- 4.0pg/mL) (p=0.003). Three patients with refractory relapse and death had much higher VEGF and bFGF values (VEGF; 420.0 +/- 81.6pg/ mL, bFGF; 85.6 +/- 3.2pg/mL). CONCLUSION: Our data suggest that the increased levels of VEGF and bFGF in bone marrow may play an important role in prognosis of childhood ALL.

BACKGROUND: Although pulmonary resection is the standard approach for the management of pulmonary metastases from soft tissue sarcoma, most of them are unresectable and chemotherapy remains the only option. The effectiveness of the cytotoxic drugs may be limited by the toxicities that occur before the therapeutic dose is reached. The regional administration of doxorubicin using pulmonary arterial perfusion in a rodent model can produce 10 to 25 times higher concentrations in the lung than systemic administration with minimal systemic toxicities. However, it is unclear whether a high concentration of doxorubicin has beneficial effects for killing cancer cells. MATERIAL AND METHOD: We studied this to evaluate the dose-dependent cytotoxic and apoptotic effects of doxorubicin on methylcholanthrene-induced rat fibrosarcoma(MCA) cells. This study examined the cytotoxicity and apoptosis-related gene expressions(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) in MCA cells after 24 hours exposure to various concentrations of doxorubicin such as 1, 5, 10, 50, and 100 micrometer. RESULT: Dose-dependent cytotoxicity was observed after 24 hours exposure to doxorubicin. However, peak apoptosis after 24 hours exposure was observed at 5 micrometer of doxorubicin. Above 5 micrometer, apoptotic activity was decreased with dose-increment. All mRNA levels of apoptosis-related genes after 24 hours exposure were up-regulated above the control level at 1 micrometer of doxorubicin and then decreased by doxorubicin dose-increment except caspase 8, which showed higher levels than the control level at 5 micrometer. Apoptosis-related protein levels were highest at 1 micrometer of doxorubicin and then decreased by doxorubicin dose-increment. However, Bax and Bcl-xL proteins steadily showed higher levels than the control throughout the different concentrations of doxorubicin. CONCLUSION: These results suggest that apoptosis is the main cytotoxic mechanism in low concentrations of doxorubicin in MCA cells and apoptosis-related genes, such as Bax, caspase 8, a can kill MCA cells, even when apoptosis is inhibited, and have its propriety for achieving much cytotoxicity against MCA cells.
Animals ; Apoptosis* ; bcl-X Protein ; Caspase 1 ; Caspase 2 ; Caspase 8 ; Doxorubicin* ; Drug Therapy ; Fibrosarcoma ; Homicide ; Lung ; Neoplasm Metastasis ; Perfusion ; Rats* ; RNA, Messenger ; Rodentia ; Sarcoma

Despite the rarity of primary bone tumors, osteosarcoma and Ewing sarcoma are the most common primary malignant bone tumors in children and adolescents. Multiagent chemotherapy regimens for neoadjuvant and adjuvant treatment remarkably improved the survival outcome for patients with osteosarcoma and Ewing sarcoma, therefore, most patients are now limb-salvage candidates. However, survival rate reached a plateau for last decades and is still unsatisfactory in the metastatic and relapse setting. Therefore, as seen in denosumab in giant cell tumor, further clinical trials based on molecular mechanism are warranted. This article reviews the current state of the art of systemic chemotherapy by focusing on the clinical heterogeneity of each subtype.
Adolescent ; Child ; Drug Therapy* ; Giant Cell Tumors ; Humans ; Osteosarcoma ; Population Characteristics ; Recurrence ; Sarcoma, Ewing ; Survival Rate ; Denosumab

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone.Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents.HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

PURPOSE: We compared the relative sensitivity and specificity between the urine cytology and fluorescence in situ hybridization (FISH) for the detection of urothelial carcinoma. MATERIALS AND METHODS: FISH was used a mixture of fluorescent labeled probes to the centromeres of chromosomes 3, 7 and 17, and band 9p21 (P16/CDKN2A gene). Washing urine specimens were analyzed from 37 patients, including 27 with a known bladder urothelial carcinoma and 10 without a history of urothelial carcinoma. The sensitivity and specificity of the FISH was compared to that of urine cytology. FISH positivity was defined as more than 2 urothelial cells with an abnormal signal copy number of any one out of 4 probes. RESULTS: In the bladder urothelial cancer group (n=27), the overall sensitivity of the urine cytology was 59.3% versus 88.9% for FISH (p=0.046). The sensitivity of urine cytology for pTa-1 (6 cases), and pT2-pT4 (11 cases) tumors were 37.5%, and 90.9%, respectively, and the sensitivity of FISH for pTa-1 (13 cases), and pT2-pT4 (11 cases) tumors were 81.3%, and 100%, respectively. The sensitivity of urine cytology were 33.3% (5 cases) for low grade tumors, and 91.7% (11 cases) for high grade tumors. The sensitivities of FISH were 80.0% (12 cases) for low grade tumors, and 100% (12 cases) for high grade tumors. FISH was significantly more sensitive than urine cytology for pTa-1 (p=0.021), low grade tumors (p=0.023) and all tumors (p=0.046). In the control group (n=10), the specificity of urine cytology and FISH was 90.0% and 100%, respectively (p=0.056). CONCLUSIONS: With these results, the sensitivity of FISH for the detection of urothelial carcinoma is superior to that of urine cytology, and the specificity of FISH and urine cytology for urothelial carcinoma are not significantly different. FISH, in particular, is more sensitive in the detection of low grade, low stage bladder tumors. Further prospective studies are required but FISH can successfully be used as supplementary methods to detect low grade, low stage urothelial tumors.
Centromere ; Fluorescence* ; Humans ; In Situ Hybridization* ; Sensitivity and Specificity ; Urinary Bladder Neoplasms ; Urinary Bladder*

No abstract available.
Glomerular Filtration Rate* ; Kidney*

A large number of studies have been performed to identify biomarkers that will allow efficient detection and determination of the precise status of a patient's disease. The use of microarrays to assess biomarker status is expected to improve prediction accuracies, because a whole-genome approach is used. Despite their potential, however, patient samples can differ with respect to biomarker status when analyzed on different platforms, making it more difficult to make accurate predictions, because bias may exist between any two different experimental conditions. Because of this difficulty in experimental standardization of microarray data, it is currently difficult to utilize microarray-based gene sets in the clinic. To address this problem, we propose a method that predicts disease status using gene expression data that are transformed by their ranks, a concept that is easily applied to two datasets that are obtained using different experimental platforms. NCI and colon cancer datasets, which were assessed using both Affymetrix and cDNA microarray platforms, were used for method validation. Our results demonstrate that the proposed method is able to achieve good predictive performance for datasets that are obtained under different experimental conditions.
Bias (Epidemiology) ; Colonic Neoplasms ; Gene Expression ; Humans ; Oligonucleotide Array Sequence Analysis ; Biomarkers

In microarray technology, many diverse experimental features can cause biases including RNA sources, microarray production or different platforms, diverse sample processing and various experiment protocols. These systematic effects cause a substantial obstacle in the analysis of microarray data. When such data sets derived from different experimental processes were used, the analysis result was almost inconsistent and it is not reliable. Therefore, one of the most pressing challenges in the microarray field is how to combine data that comes from two different groups. As the novel trial to integrate two data sets with batch effect, we simply applied standardization to microarray data before the significant gene selection. In the gene selection step, we used new defined measure that considers the distance between a gene and an ideal gene as well as the between-slide and within-slide variations. Also we discussed the association of biological functions and different expression patterns in selected discriminative gene set. As a result, we could confirm that batch effect was minimized by standardization and the selected genes from the standardized data included various expression pattems and the significant biological functions.
Bias (Epidemiology) ; Computational Biology ; Dataset* ; Genes, vif ; RNA