FLASH radiotherapy (FLASH RT) is a technique to deliver ultra-high dose rate in a fraction of a second. Evidence from experimental animal models suggest that FLASH RT spares various normal tissues including the lung, gastrointestinal track, and brain from radiation-induced toxicity (a phenomenon known as FLASH effect), which is otherwise commonly observed with conventional dose rate RT. However, it is not simply the ultra-high dose rate alone that brings the FLASH effect. Multiple parameters such as instantaneous dose rate, pulse size, pulse repetition frequency, and the total duration of exposure all need to be carefully optimized simultaneously. Furthermore it is critical to validate FLASH effects in an in vivo experimental model system. The exact molecular mechanism responsible for this FLASH effect is not yet understood although a number of hypotheses have been proposed including oxygen depletion and less reactive oxygen species (ROS) production by FLASH RT, and enhanced ability of normal tissues to handle ROS and labile iron pool compared to tumors. In this review, we briefly overview the process of ionization event and history of radiotherapy and fractionation of ionizing radiation. We also highlight some of the latest FLASH RT reviews and results with a special interest to neurocognitive protection in rodent model with whole brain irradiation. Lastly we discuss some of the issues remain to be answered with FLASH RT including undefined molecular mechanism, lack of standardized parameters, low penetration depth for electron beam, and tumor hypoxia still being a major hurdle for local control. Nevertheless, researchers are close to having all answers to the issues that we have raised, hence we believe that advancement of FLASH RT will be made more quickly than one can anticipate.

PURPOSE: Adriamycin(R) is one of the most commonly used drugs in the treatment of breast cancer. This study was performed to understand the molecular mechanisms of drug resistance in breast cancer cells. MATERIALS AND METHODS: We have analyzed the MCF-7 breast cell line and its adriamycin-resistant variants, MCF-7/ADR using human 10 K element cDNA microarrays. RESULTS: We defined 68 genes that were up-regulated (14 genes) or down-regulated (54 genes) in adriamycin resistant breast cancer cells. Several genes, such as G protein-coupled receptor kinase 5, phospholipase A2, guanylate cyclase 1, vimentin, matrix metalloproteinase 1 are up-regulated in drug resistant cells. Several genes, such as interferon, alpha-inducible protein 27, forkhead box M1, mitogen-activated protein kinase 6, regulator of mitotic spindle assembly 1 and tumor necrosis factor superfamily are down-regulated in adriamycin resistant cells. The altered expression of genes observed in microarray was verified by RT-PCR. CONCLUSION: These findings show that cDNA microarray analysis can be used to obtain gene expression profiles reflecting the effect of anticancer drugs on breast cancer cells. Such data may lead to the assigning of signature expression profiles of drug-resistant tumors which may help predict responses to drugs and assist in the design of tailored therapeutic regimens to overcome drug resistance.
Breast Neoplasms* ; Breast* ; Cell Line ; DNA, Complementary* ; Doxorubicin* ; Drug Resistance ; Gene Expression* ; Guanylate Cyclase ; Humans ; Interferons ; Matrix Metalloproteinase 1 ; Mitogen-Activated Protein Kinase 6 ; Oligonucleotide Array Sequence Analysis* ; Phospholipases A2 ; Phosphotransferases ; Spindle Apparatus ; Transcriptome* ; Tumor Necrosis Factor-alpha ; Vimentin

PURPOSE: Gastric cancer is one of the most prevalent cancers worldwide. 5-fluorouracil (5-FU) and cisplatin are the most commonly used drugs for the treatment of gastric cancer. However, a significant number of tumors often fail to respond to chemotherapy. MATERIALS AND METHODS: To better understand the molecular mechanisms underlying drug resistance in gastric cancer the gene expression in gastric cancer cells, which were either sensitive or resistant to 5-FU and cisplatin, were examined using cDNA microarray analysis. To confirm the differential gene expression, as determined using the microarray, semiquantitative RT-PCR was performed on a subset of differentially expressed cDNAs. RESULTS: 69 and 45 genes, which were either up-regulated (9 and 22 genes) or down-regulated (60 and 25 genes), were identified in 5-FU- and cisplatin-resistant cells, respectively. Several genes, such as adaptor-related protein complex 1 and baculoviral IAP repeat-containing 3, were up-regulated in both drug-resistant cell types. Several genes, such as the ras homolog gene family, tropomyosin, tumor rejection antigen, protein disulfide isomerase-related protein, melanocortin 1 receptor, defensin, cyclophilin B, dual specificity phosphatase 8 and hepatocyte nuclear factor 3, were down-regulated in both drug-resistant cell types. CONCLUSION: These findings show that cDNA microarray analysis can be used to obtain gene expression profiles that reflect the effect of anticancer drugs on gastric cancer cells. Such data may lead to the assigning of signature expression profiles of drug-resistant tumors, which may help predict responses to drugs and assist in the design of tailored therapeutic regimens to overcome drug resistance.
Adaptor Protein Complex 1 ; Cisplatin* ; Cyclophilins ; DNA, Complementary* ; Drug Resistance ; Drug Therapy ; Dual-Specificity Phosphatases ; Fluorouracil* ; Gene Expression* ; Hepatocytes ; Humans ; Oligonucleotide Array Sequence Analysis* ; Receptor, Melanocortin, Type 1 ; Stomach Neoplasms* ; Transcriptome ; Tropomyosin

Krukenberg tumor of the ovary, originally described by Krukenberg as "Fibrosarcoma ovarii mucocellulare carcinomatodes", characterized as an infiltrative mucinous carcinoma of predominant signet-ring cell type, almost metastasize from gastrointestinal tract, is not common tumor. In recent years, we have experienced 2 cases of Krukenberg tumors on both ovaries metastasis from the stomach, and report these cases with brief review of the literatures.
Adenocarcinoma, Mucinous ; Female ; Gastrointestinal Tract ; Krukenberg Tumor* ; Neoplasm Metastasis ; Ovary ; Stomach ; Stomach Neoplasms

PURPOSE: IL-10 and IFN-gamma are amongst important cytokines, which are thought to have influence on organ transplantation outcome. The aim of this study was to investigate the IL-10 and IFN-gamma gene polymorphisms in Koreans, and their association with renal transplantation outcome. METHODS: Three SNP sites (-1082 G/A, -819 C/T, -592 C/A) of IL-10 promoter region and CA repeats in intron 1 of IFN-gamma gene were analyzed using PCR-single strand conformation polymorphism (SSCP) and direct sequencing methods in 73 controls and 164 kidney allograft recipients. Association between polymorphisms of these genes and transplantation outcome was analyzed using chi square test or Fisher's exact test. RESULTS: The allele frequencies of the IL-10 and IFN-gamma genes showed no significant differences between the control and patient groups. The frequencies of IL-10 and IFN-gamma high producer alleles were markedly lower than those of Caucasians. The incidence of multiple acute rejection episodes was higher in IL-10low producer (-1082 AA) than intermediate producer (-1082 GA) group (8.6% vs 0%), and in IFN-gamma high producer ([CA]12 positive) than low producer ([CA]12 negative) group (11.9% vs 6.6%). The incidence of chronic renal allograft dysfunction was lower in IL-10 intermediate producer than low producer group (7.7% vs 18.0%), and also lower in the combination of IL-10 intermediate/IFN-gamma low producer type than in other combinations (0% vs 18.2%). However, all these differences were not statistically significant. CONCLUSION: IL-10 and IFN-gamma have little influence on renal transplantation outcome in Koreans, probably due to quite limited polymorphisms of these genes in this population. The results of this study would be useful as basic data for renal transplantation in Koreans.
Alleles ; Allografts* ; Cytokines ; Gene Frequency ; Humans ; Incidence ; Interleukin-10* ; Introns ; Kidney Transplantation* ; Kidney* ; Organ Transplantation ; Promoter Regions, Genetic ; Transplants

No abstract available.
Estrogens, Conjugated (USP)* ; Hypersplenism*

PURPOSE: Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 have been shown to play important roles in allograft rejection of various organs. This study was performed to evaluate the association of TNF-alpha and TGF-beta1 genes and renal allograft dysfunction. METHODS: Five TNF-alpha ( 1,031 T/C, 863 C/A, 857 C/T, 308 G/A, 238 G/A) and two TGF-beta1 (codon 10 T/C, codon 25 G/C) single nucleotide polymorphism (SNP) sites were studied using PCR-SSCP and PCR-RFLP methods in 100 controls and 165 patients underwent renal transplantation. For the TGF-beta1 gene, we also studied the polymorphism of donors. RESULTS: The allele frequencies of each SNP sites in controls were not different from those of patients. The phenotype frequency of TNF-alpha high producer type, 308 A was significantly higher in the patients with recurrent acute rejection episodes (REs) compared with patients with no or one RE (38.5% vs. 9.2%, P=0.007). The frequency of TGF-beta1 low producer genotype, codon 10 CC was also significantly higher in the patients with recurrent REs (53.8% vs. 22.4%, P=0.029). Analysis of chronic renal allograft dysfunction (CRAD) revealed that the TGF-beta1 high producer type, codon 10 T allele in donors was associated with CRAD (66.7% vs. 48.2%, P=0.043). This association was significant only among patients with recurrent REs. Occurrence of CRAD was not influenced by TGF-beta1 polymorphisms in the patients. CONCLUSION: These results would be useful for predicting high risk group for acute rejection or CRAD in renal transplantation and might be useful for implying individualized immunosuppressive therapy.
Alleles ; Allografts* ; Codon ; Gene Frequency ; Genotype ; Humans ; Kidney Transplantation ; Phenotype ; Polymorphism, Single Nucleotide ; Tissue Donors ; Transforming Growth Factor beta1* ; Transforming Growth Factors ; Tumor Necrosis Factor-alpha*

No abstract available.
Apoptosis* ; Placenta Previa* ; Placenta*

Benign cystic teratoma is the common ovarian tumor, and the incidence reported about 20%. Malignant transformation of mature cystic teratoma of the ovary is rare, which can develop with an incidence of less than 2%. The most common malignant tumor arising in mature cystic teratoma is squamous cell carcinoma which account for 75-85%, but vary rare cases of anaplastic carcinoma arising from mature cystic teratoma has been reported all over the world and prognosis of this malignant tumor was poor. No case of anaplastic carcinoma has been reported before in Korea. We experienced a case of anaplastic carcinoma arising from mature cystic teratoma of the ovary and report our case with a brief review of literature.
Carcinoma* ; Carcinoma, Squamous Cell ; Female ; Incidence ; Korea ; Ovary* ; Prognosis ; Teratoma*

Mucosal-associated lymphoid tissue(MALT) lymphoma is derived from the marginal zone B-cell compartment and can be found at wide variety of extranodal sites, most frequently at the gastrointestinal sites. Recent clinicopathologic studies suggest a relationship between MALT lymphoma and chronic inflammatory disorders, such as Helicobacter pylori infection in stomach or autoimmune disorders, such as Sj gren's syndrome in salivary glands. Primary gastrointestinal MALT lymphoma most commonly arises in the stomach and less often in the small and large intestine. Recently we experienced a case who had MALT lymphoma and tuberculous enteritis at the same site (jejunum) confirmed by exploratory laparotomy.
B-Lymphocytes ; Enteritis* ; Helicobacter pylori ; Intestine, Large ; Intestine, Small ; Jejunum* ; Laparotomy ; Lymphoma* ; Lymphoma, B-Cell, Marginal Zone ; Salivary Glands ; Stomach