ABSTRACT
PURPOSE: We retrospectively investigated the effect of irradiation using helical tomotherapy in recurrent pelvic tumors that underwent prior irradiation. MATERIALS AND METHODS: Fourteen patients with recurrent pelvic tumors consisting of rectal cancer (57.1%), cervical cancer (35.7%) and cancer with an unknown origin (7.1%) were treated with tomotherapy. At the time of irradiation, median tumor size was 3.5 cm and 7 patients complained of pain originating from a recurrent tumor. The median radiation dose delivered to the gross tumor volume, clinical target volume, and planning target volume was 50 Gy, 47.8 Gy and 45 Gy, respectively and delivered at 5 fractions per week over the course of 4 to 5 weeks. Treatment response and duration of local disease control were evaluated using the Response Evaluation Criteria in Solid Tumors (ver. 1.0) and the Kaplan-Meyer method. Treatment-related toxicities were assessed through Common Terminology Criteria for Adverse Events (ver. 3.0). RESULTS: The median follow-up time was 17.3 months, while the response rate was 64.3%. Symptomatic improvement appeared in 6 patients (85.7%). The median duration time of local disease control was 25.8 months. The rates of local failure, distant failure, and synchronous local and distant failure were 57.1%, 21.4%, and 7.1%, respectively. Acute toxicities were limited in grade I or II toxicities, except for one patient. No treatment related death or late toxicity was observed. CONCLUSION: Helical tomotherapy could be suggested as a feasible palliative option in recurrent pelvic tumors with prior radiotherapy. However, to increase treatment effect and overcome the limitation of this outcome, a large clinical study should be performed.
Subject(s)
Humans , Follow-Up Studies , Radiotherapy, Intensity-Modulated , Rectal Neoplasms , Retrospective Studies , Tumor Burden , Uterine Cervical NeoplasmsABSTRACT
OBJECTIVE: Comparison of protein expression by two-dimensional gel electrophoresis (2-DE) in normal myometrium and uterine leiomyoma in Korean women. METHODS: Normal myometrium and uterine leiomyoma tissues were solubilized with 2-DE buffer and the first dimension of PROTEAN IEF CELL, isoelectric focusing (IEF), was performed using pH4-8 linear IPG strips of 17 cm. And then running 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS- PAGE) and sliver stain. Scanned image analyzed using PDQuest 2-D softwareTM. Protein spot spectrum was identified by assisted laser desorption/ionization-time of fighting (MALDI-TOF) and the protein mass spectrums identification were performed by searching protein databases of Swiss-prot/TrEMBL, Mascot and MS-FIT. RESULTS: In this study, we found 17 up-regulated proteins (phosphate carrier protein, 60 kDa heat shock protein, acidic calcium-independent, glutathione transferase omega, chloride intracellular channel 4, Ras-related protein Rab-11B, phosphatidylinositol transfer protein alpha isoform, type II keratin subunit protein, Cofilin 2 isoform 1, transgelin, ATP carrier protein, alpha-catenin homolog, parkinson disease 2, apo-cellular retinoic acid binding protein II, osteoglycin preproprotein, proteasome activator subunit 1 isoform, Unnamed protein) and 7 down-regulated proteins (Serum amyloid P component, annexin IV, alpha 1 actin precursor, hypoxanthine-guanine phosphoribosyltransferase, tumor necrosis factor receptor superfamily member EDAR precursor, peroxiredoxin 2, translation elongation factor EF-Tu precursor) between myometrium and leiomyoma. CONCLUSION: 2-DE offer total protein expression between normal myometrium and uterine leiomyoma, and searching of differently expressed protein for the diagnostic markers of leiomyoma.
Subject(s)
Animals , Female , Humans , Mice , Actins , Adenosine Triphosphate , alpha Catenin , Annexin A4 , Carrier Proteins , Cofilin 2 , Databases, Protein , Electrophoresis, Gel, Two-Dimensional , Electrophoresis, Polyacrylamide Gel , Glutathione Transferase , Heat-Shock Proteins , Hypoxanthine Phosphoribosyltransferase , Isoelectric Focusing , Keratins, Type II , Leiomyoma , Myometrium , Parkinsonian Disorders , Peptide Elongation Factor Tu , Peptide Elongation Factors , Peroxiredoxins , Phospholipid Transfer Proteins , Proteasome Endopeptidase Complex , Receptors, Tumor Necrosis Factor , Running , Serum Amyloid P-Component , Sodium Dodecyl Sulfate , TretinoinABSTRACT
OBJECTIVE: A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG), has been known to possess anti-diabetes, anti-hypertension and anti-cancer properties. In this study, we investigated the anticancer effects of EGCG on human ovarian cancer cell lines. The growth inhibitory mechanism(s) and regulation of cell cycle-related proteins by EGCG were also evaluated. METHODS: To carry out cell counting assay to observe the anti-proliferative effects, we treated 25, 50, and 100 uM EGCG to both ovarian cancer cell lines SKOV-3 and OVCAR-3, respectively. Also, we treated EGCG to PA-1 cells with 6.25, 12.5 and 25 uM, respectively. Six days later, we examined the characteristics of apoptosis and changes in cell cycle regulation by cell counting assay, Annexin V-FITC staining and DNA fragmentation assay, and FACS analysis. In addition, protein and gene expression patterns in SKOV-3 cell were investigated by using cell cycle cDNA chip, RT-PCR, and Western blot analyses. RESULTS: Inhibition of cell growth by cell counts showed in SKOV-3 cells with 48.8%, 82.5%, 99.2% after six days of the treatment with 25, 50, 100 uM of EGCG, respectively. OVCAR-3 cells showed 53.9%, 84.8%, and 97.7% growth inhibition patterns. And PA-1 cells showed 17.1%, 48.4%, and 74.1%, as compared to control. When SKOV-3 cells were tested for EGCG-induced apoptosis, apoptotic cells were observed with 8.6, 11.4, and 23.3-fold at 25, 50, 100 uM EGCG, respectively. And PA-1 cells showed 1.7, 2.4, and 4.2-fold, as compared to control. In contrast, OVCAR-3 did not show EGCG-induced apoptosis. When SKOV-3 cells were tested for their gene expression using cell cycle cDNA chip after treatment with 24.5 uM of EGCG, up-regulations of p21, Bax and cyclin G were shown, while down-regulations of CDK6, E2F-4, and cyclin A were shown. In Western blot assay, up-regulations of Bax and p21 proteins were shown, while down- regulations of cyclin D1, Bcl-XL, Rb, CDK2, E2F-1, E2F-4, PCNA proteins were shown. CONCLUSION: These data support that EGCG can inhibit ovarian cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of gene and protein expressions. Thus, EGCG likely provides an additional option for a new and potential drug approach for ovarian cancer.
Subject(s)
Humans , Apoptosis , Blotting, Western , Cell Count , Cell Cycle , Cell Cycle Checkpoints , Cell Line , Cyclin A , Cyclin D1 , Cyclin G , DNA Fragmentation , DNA, Complementary , Gene Expression , Ovarian Neoplasms , Proliferating Cell Nuclear Antigen , Social Control, Formal , TeaABSTRACT
OBJECTIVE: The molecular pathology of cervical cancer associated with human papillomavirus infection is presently unclear. In an effort to clarify the multiple interactions of a number of genes involved in cervical carcinogenesis, the gene expression profiles and pathogenic cellular processes between human cervical squamous cell carcinoma and normal cervix were investigated by mRNA differential display and the Gene Ontology analysis. METHODS: Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, The Catholic University of Korea. The disease status was assigned according to the International Federation of Gynecology and Obstetrics. The squamous cell carcinoma tissue samples of 3 patients invasive cancer stage II (1), IV (2) were investigated by mRNA differential display. As a control, we used a common reference that was mixed with equal amount of RNA obtained from 17 normal cervix to obtain variation- independent control. Also, we constructed hierarchical functional structures using gene ontology. Then, the specific function groups were correlated with differential gene expression profiles. In addition, specific gene expression patterns in several tissue samples were investigated by using DDRT-PCR analysis. RESULTS: Differentially expressed 191 genes were identified in tumor samples. Of these genes, 128 were up-regulated and 63 were down-regulated above 1.5-fold. The gene expression profiles were classified into 46 mutually dependent function sets and organized into sub-function sets depending on the cervical cancer pathway, suggesting the potentially significant genes of unknown function affected by carcinogenesis pathway. The genes related to metabolism, signal transduction, and chaperon activity were significantly up-regulated. In contrast, significant down-regulations were shown in nucleic acid binding activity, tumor suppressor and structural activity. Reliable gene expression data shows the validation of profiling method for studying the cervical cancer-specific pathway. CONCLUSION: The specific functions assigned to each expressed gene were correlated with gene ontology for the establishment of a powerful cervical carcinogenesis pathway. The results suggest that the differentially regulated cellular process profiles have an important impact on discovery of pathogenic pathway in human cervical squamous cell carcinoma and provide the potentially significant genes of unknown function. Also, the gene ontology analysis can overcome the complexity of the expression profiles of mRNA differential display via a cellular process level approach. Thereby, a valuable prognostic candidate gene with real relevance to disease-specific pathogenesis can be found at the cellular process levels.