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ABSTRACT: The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors.
We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients.
The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. ≤90 Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed.
Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.
Radiation oncology journal. 03/2013; 31(1):18-24.
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ABSTRACT: Previous studies have demonstrated that calcium channel blockers have protective effects on damaged brains. In the present study, the protective effect of the calcium channel blocker nicardipine against rotenone‑induced apoptosis in SH‑SY5Y human neuroblastoma cells was investigated, focusing on mitogen‑activated protein kinases (MAPKs) and caspase (CASP)‑mediated apoptotic events. Nicardipine was found to decrease rotenone‑induced apoptosis through 4,6‑diamidino‑2‑phenylindole staining and the terminal deoxynucleotidyl transferase‑mediated dUTP nick end‑labeling assay. In addition, nicardipine was identified to inhibit rotenone‑induced elevation of intracellular Ca2+ concentration measured using the Fluo‑4 AM fluorescent dye. Rotenone increased phosphorylation of c‑Jun NH2‑terminal kinase (JNK) and p38 MAPK, whereas nicardipine blocked these increases. Nicardipine also prevented downregulation of B‑cell CLL/lymphoma 2 and upregulation of Bcl2‑associated X protein by rotenone. Furthermore, nicardipine abrogated cleavage of CASP9 and 3 and poly (ADP‑ribose) polymerase‑1 by rotenone and CASP3 enzyme activity in rotenone‑treated cells. These results indicate that nicardipine exerts a protective effect against rotenone‑induced apoptosis in SH‑SY5Y cells, inhibiting phosphorylation of JNK and p38 MAPK and activation of CASPs.
Molecular Medicine Reports 01/2013; · 0.42 Impact Factor
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ABSTRACT: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta (TGFβ) superfamily with well-described functions in bone formation. Although disrupted BMP signaling in tumor development has been investigated, a genetic association for BMP3 in papillary thyroid cancer (PTC) has remained largely unexplored. In this study, we investigated whether BMP3 single nucleotide polymorphisms (SNPs) are associated with the development of PTC and its clinicopathological features. A total of 103 PTC patients and 324 control subjects were enrolled. One promoter SNP (rs13138132; -1919C/A) and one missense mutation (rs3733549; Arg192Gln) in BMP3 were genotyped by direct sequencing. SNPStats, SNPAnalyzer, Helixtree and Haploview version 4.2 were used to evaluate the genetic data. Multiple logistic regression models were used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and P-values. The missense SNP (rs3733549) was weakly associated with the development of PTC in a codominant model (AA vs. GG; P=0.017) and a recessive model (AA vs. GG/GA; P=0.023). Additionally, in an analysis according to clinicopathological features, rs13138132 was significantly associated with extra-thyroidal invasion in a codominant model (CA vs. CC; P=0.006) and a dominant model (CA/AA vs. CC; P=0.0023). We also identified that the frequency of the A allele in the promoter SNP (rs13138132) was increased in PTC patients with extrathyroidal invasion (P=0.004). Our data suggest that rs3733549 in BMP3 is associated with the development of PTC and that the A allele of rs13138932 in BMP3 is a risk factor for extrathyroidal invasion.
Oncology letters 01/2013; 5(1):336-340. · 0.11 Impact Factor
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ABSTRACT: Ten topics were chosen among major clinical research achievements in gynecologic oncology in 2012. For ovarian cancer, comprehensive review of the history of bevacizumab studies was followed by poly adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors and other molecular targeted agents such as epidermal growth factor receptor tyrosine kinase inhibitor and AMG 386. For the development of genomic study in gynecologic cancers, BRCA and DICER1 mutations were covered in epithelial and nonepithelial ovarian cancer, respectively. For endometrial cancer, targeted agents including mammalian target of rapamycin (mTOR) inhibitors and bevacizumab were discussed. Radiation therapy "sandwiched" between combination chemotherapy schedules for the treatment of uterine papillary serous carcinoma was also reviewed. Preoperative prediction of lymph node metastasis, definition of low-risk group, and recurrence and survival outcomes of laparoscopic approaches were addressed. For cervical cancer, we reviewed long-term benefit of human papillomavirus test and efficacy of paclitaxel/carboplatin versus paclitaxel/cisplatin in stage IVB, persistent or recurrent disease. In addition, the effect of three dimensional image-based high-dose rate brachytherapy was also reviewed. For vulvar cancer, the diagnostic value of sentinel lymph node biopsy was discussed. For breast cancer, positive results of three outstanding phase III randomized clinical trials, CLEOPATRA, EMILIA, and BOLERO-2 were introduced. Lastly, updates of major practice guidelines were summarized.
Journal of Gynecologic Oncology 01/2013; 24(1):66-82. · 1.49 Impact Factor
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ABSTRACT: BACKGROUND: To analyze treatment outcomes and patterns of recurrence, and to examine the impact of adjuvant postoperative radiotherapy (PORT) after esophagectomy in esophageal squamous cell carcinoma (SqCC) regarding the status of circumferential resection margin (CRM). PATIENTS AND METHODS: We performed a retrospective review of esophageal cancer patients operated in Seoul National University Hospital between 2003 and 2010. Pathologically proven T3 SqCC patients with written reports mentioning the status of CRM were selected. Fifty-nine out of 71 patients (83.1%) had CRM+. Twenty-eight patients had radiotherapy in CRM+ and CRM-, respectively. The median follow-up period was 17.1 months (range: 5.2-63.1). RESULTS: Median survival and 2-year overall survival were 13.8 months and 41.9% in CRM+, and 27.3 months and 74.1% in CRM-, respectively. Loco-regional relapse-free survival (LRRFS) rate at 2 years was 33.6% and 74.1% in each groups (P = 0.029). Loco-regional recurrence was the major pattern of failure in CRM+. PORT did not improve LRRFS. CONCLUSION: The esophageal SqCC patients with CRM+ after resection showed worse LRRFS. This finding validated the prognostic value of CRM status. Nevertheless, we failed to demonstrate the benefits of adjuvant PORT in CRM+. This might suggest the necessity of neoadjuvant therapy to decrease the CRM+ rate after esophagectomy. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.
Journal of Surgical Oncology 12/2012; · 2.10 Impact Factor
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ABSTRACT: The current study was conducted in order to evaluate the clinical outcome of radical radiotherapy (RT) with or without chemotherapy for elderly patients with stage III non-small cell lung cancer (NSCLC).
Between 1990 and 2010, 125 patients, aged 70 years or more, received radical RT with or without chemotherapy for treatment of stage III NSCLC. We reviewed the patients' prognostic factors, including comorbidities. Comorbidity status was evaluated using a simplified comorbidity score (SCS). Of the patients reviewed, 82 received radical RT alone, whereas the other 43 patients underwent chemoradiotherapy (CRT). A platinum-based chemotherapy regimen was most commonly used (42/43).
The two-year overall-survival (OS) and progression-free survival (PFS) rates were 32.2% and 21.8%, respectively. SCS was the independent prognostic factor for OS. In the frail elderly subgroup with a SCS of ≥10, CRT demonstrated a significant difference in PFS, but not in OS. In contrast, OS and PFS following CRT were significantly superior to RT in the fit elderly subgroup with a SCS of <10. The incidence of severe pulmonary toxicities in the frail elderly subgroup was significantly higher than that in the fit elderly subgroup.
Multiple comorbidities evaluated according to the SCS are related to poor OS in elderly patients with stage III NSCLC. CRT improved clinical outcome when compared to RT in the fit elderly subgroup, however, the gain from this treatment was negated in the frail elderly subgroup with multiple comorbidities. Therefore, evaluation of comorbidity is necessary in order to determine whether chemotherapy should be combined with RT in elderly patients with stage III NSCLC.
Cancer Research and Treatment 12/2012; 44(4):242-50.
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ABSTRACT: In this study, we investigated whether genetic polymorphisms of the interferon gamma (IFNG) gene were associated with the susceptibility of ossification of the posterior longitudinal ligament (OPLL) in the Korean population. To observe the association between the IFNG gene and the susceptibility of OPLL, we genotyped 135 OPLL patients and 222 control subjects for a single nucleotide polymorphism (SNP, rs2430561) and a microsatellite (CA(n) repeats, rs3138557) located in the first intron of the IFNG gene, using the direct sequencing and gene scan method. The numbers of microsatellites (CA(13) and CA(15)) were significantly changed in the OPLL patients. A combined analysis of the genotype of rs2430561 and the number of microsatellites revealed that the OPLL was associated with frequencies of CA(13)-AA, CA(15)-AA and CA(15)-AT. Our results suggest that the IFNG gene may be one of the factors determining the OPLL in the Korean population. However, larger collaborative and biological studies are needed to confirm these results.
Immunological Investigations 10/2012; · 1.47 Impact Factor
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Jaesoon Joo,
Soojeong Lee,
Seong-Su Nah,
Young Ock Kim,
Duk-Soo Kim,
Se-Hoon Shim,
Young Hwangbo,
Hyung-Kee Kim,
Jun-Tack Kwon,
Jong Woo Kim,
Ho-Yeon Song, Hak-Jae Kim
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ABSTRACT: Mice treated with MK-801, a non-competitive antagonist of the N-methyl-d-aspartic (NMDA) acid receptor, are important animal models for schizophrenia studies. In the present study, we compared protein expression levels in the hippocampus of mice treated with MK-801 (0.6 mg/kg) or saline once daily for 7 days. Changes in the proteome were detected by two-dimensional electrophoresis, and the six proteins exhibiting differential expression were identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Down-regulation of one of these proteins, Lasp1 (LIM and SH3 protein 1), in MK-801-treated mice was confirmed by western blotting and immunohistochemical analyses. Lasp1 is a multidomain protein that may recruit signaling molecules to the actin-based cytoskeleton and is known to concentrate in synaptic sites of hippocampal neurons. We next investigated whether polymorphisms in the human LASP1 gene were associated with schizophrenia in the Korean population. A single-nucleotide polymorphism in the LASP1 gene promoter region was associated with schizophrenia susceptibility. Our results suggest that LASP1 might be associated with NMDA receptor antagonism and schizophrenia susceptibility and, thus, might be involved in the pathophysiology of schizophrenia.
Journal of psychiatric research 10/2012; · 3.72 Impact Factor
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ABSTRACT: The present study was performed to assess the usefulness of involved-field irradiation and the impact of (18)F-fluorodeoxyglucose-positron emission tomography-based staging on treatment outcomes in limited-stage small cell lung cancer.
Eighty patients who received definitive chemoradiotherapy for limited-stage small cell lung cancer were retrospectively analyzed. Fifty patients were treated with involved-field irradiation, which means that the radiotherapy portal includes only clinically identifiable tumors. The other 30 patients were irradiated with a comprehensive portal, including uninvolved mediastinal and/or supraclavicular lymph nodes, so-called elective nodal irradiation. No significant difference was seen in clinical factors between the two groups.
At a median follow-up of 27 months (range, 5-75 months), no significant differences were observed in 3 year overall survival (44.6 vs. 54.1%, P= 0.220) and 3 year progression-free survival (24.4 vs. 42.8%, P= 0.133) between the involved-field irradiation group and the elective nodal irradiation group, respectively. For patients who did not undergo positron emission tomography scans, 3 year overall survival (29.3 vs. 56.3%, P= 0.022) and 3 year progression-free survival (11.0 vs. 50.0%, P= 0.040) were significantly longer in the elective nodal irradiation group. Crude incidences of isolated nodal failure were 6.0% in the involved-field irradiation group and 0% in the elective nodal irradiation group, respectively. All isolated nodal failures were developed in patients who had not undergone positron emission tomography scans in their initial work-ups.
If patients did not undergo positron emission tomography-based staging, the omission of elective nodal irradiation resulted in impaired survival outcomes and raised the risk of isolated nodal failure. Therefore, involved-field irradiation for limited-stage small cell lung cancer might be reasonable only with positron emission tomography scan implementation.
Japanese Journal of Clinical Oncology 07/2012; 42(10):948-54. · 1.78 Impact Factor
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ABSTRACT: This study was to evaluate the treatment outcomes and prognostic factors of patients treated with salvage radiotherapy for the treatment of isolated lymph node recurrence of cervical cancer.
Between 1990 and 2009, 22 cervical cancer patients with lymph node recurrence who had previously undergone radical hysterectomy and pelvic lymph node dissection were treated with salvage radiotherapy with (n=18) or without (n=4) chemotherapy. Of the 22 patients, 10 had supraclavicular lymph node recurrence, 9 had para-aortic lymph node, and 3 had inguinal lymph node. The median total radiotherapy dose was 60 Gy (range, 40 to 70 Gy). Initial pathologic findings, latent period to lymph node recurrence and other clinical parameters such as squamous cell carcinoma antigen (SCC-Ag) level and concurrent chemotherapy were identified as prognostic factors for survival.
The median follow-up period after salvage radiotherapy was 31.2 months (range, 12.1 to 148.9 months). The 5-year progression-free and overall survival rates of all patients were 32.7% and 30.7%, respectively. Concurrent chemoradiotherapy (p=0.009) and longer latent period to lymph node recurrence (>18 months vs. ≤18 months, p=0.019) were significant predictors of progression-free survival and SCC-Ag level at the time of recurrence (>8 ng/dL vs. ≤8 ng/dL, p=0.008) and longer latent period to lymph node recurrence (p=0.040) for overall survival. Treatment failure after salvage radiotherapy occurred in 14 (63.6%) for the 22 patients (in field, 2; out of field, 10; both in and out field, 2). Grade 3 acute skin (n=2) and hematologic toxicity (n=1) developed in 3 patients.
For isolated lymph node recurrence of cervical cancer, salvage radiotherapy with concurrent chemotherapy should be considered, especially in patients with a long-term progression-free period.
Journal of Gynecologic Oncology 07/2012; 23(3):168-74. · 1.49 Impact Factor
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ABSTRACT: This study investigated the efficacy and toxicity associated with consolidation chemotherapy using paclitaxel and carboplatin after concurrent chemoradiation (CCR) in cervical cancer patients.
From a total of 37 patients, 19 with International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IIA cervical cancer (group 1) underwent surgery followed by consolidation chemotherapy after CCR, and 18 with stage IIB-IVA disease (group 2) received consolidation chemotherapy after primary CCR. Three cycles of chemotherapy using paclitaxel (135 mg/m(2)) and carboplatin (AUC 5.0) were administered every 3 weeks for CCR therapy, and three cycles of consolidation chemotherapy using paclitaxel (175 mg/m(2)) and carboplatin (AUC 5.0) were used every 3 weeks after CCR.
The complete and partial response rates were 77.8% and 22.2% in group 2. Moreover, the 3-year progression-free and overall survival rates were 62.7% and 90.9% in group 1, and 51.9% and 60% in group 2, respectively. The most common grade 3 or 4 hematologic toxicities observed were leukopenia (group 1, 10.5%; group 2, 13.0%) and neutropenia (group 1, 7.0%; group 2, 14.8%), and grade 3 or 4 diarrhea (group 1, 1.8%) and febrile illness (group 2, 1.9%) were the most frequently observed non-hematologic toxicities. When we compared these results with previous reports, consolidation chemotherapy after CCR using paclitaxel and carboplatin revealed a relatively lower complete response rate (77.8% vs. 87-100%, respectively) and shorter progression-free survival (51.9-62.7% vs. 81-86%, respectively) and overall survival (60-90.9% vs. 81-95%, respectively) in spite of similar toxicity findings.
Due to low efficacy results, consolidation chemotherapy using paclitaxel and carboplatin after CCR is not a feasible treatment regimen for high-risk early-stage or locally advanced cervical cancer.
Cancer Research and Treatment 06/2012; 44(2):97-103.
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Hak-Jae Kim,
Chi-Yong Eom,
Joseph Kwon,
Jaesoon Joo,
Sujeong Lee,
Seong-Su Nah,
Il-Chul Kim,
Ik-Soon Jang,
Young-Ho Chung,
Seung Il Kim,
Joo-Ho Chung,
Jong-Soon Choi
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ABSTRACT: A decreased production of interferon gamma (IFNG) has been observed in acute schizophrenia. In order to explore the possible relationship between IFNG and schizophrenia, we attempted to analyze the differentially expressed proteins in the brains of interferon-gamma knockout (Ifng-KO) mice. Five upregulated and five downregulated proteins were identified with 2D gels and MALDI-TOF/TOF MS analyses in Ifng-KO mouse brain. Of the identified proteins, we focused on creatine kinase brain (CKB) and triose phosphate isomerase 1 (TPI1). Consistent with the proteomic data, reverse transcriptase-mediated PCR, immunoblotting, and immunohistochemistry analyses confirmed that the levels of gene expressions of Ckb and Tpi1 were downregulated and upregulated, respectively. When we analyzed the genetic polymorphisms of the single nucleotide polymorphisms (SNPs) of their human orthologous genes in a Korean population, the promoter SNPs of CKB and TPI1 were weakly associated with schizophrenia. In addition, IFNG polymorphisms were associated with schizophrenia. These results suggest that IFNG and proteins affected by IFNG may play a role in the pathogenesis of schizophrenia.
Proteomics 05/2012; 12(11):1815-29. · 4.43 Impact Factor
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ABSTRACT: To investigate the effects of Panax ginseng (PG) on SH-SY5Y human neuroblastoma cells, we profiled gene expressions of both normal and PG-treated groups using cDNA microarray.
We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays to determine the effect on PG-induced cytotoxicity. The gene expression profiles
in normal group were compared to PG-treated group using 24K human cDNA microarray. MTT assay showed that PG was not cytotoxic
at the concentrations of 1–100 μg/mL in SH-SY5Y cells. Consequently, 210 genes exhibited differential expression levels between
normal and PG-treated groups through cDNA microarray analysis, and it was found that 52 of the 210 genes were up-regulated
while 146 of them were down-regulated by two-fold. PG may induce changes in the expression of genes in SH-SY5Y cells possibly
relevant to signal transduction and cellular development. These results help to further understand the molecular framework
of PG as a signal transduction inducer of neuronal cells.
Keywords
Panax ginseng
-SH-SY5Y-cDNA microarray
Molecular and Cellular Toxicology 04/2012; 6(3):219-227. · 0.88 Impact Factor
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ABSTRACT: Kawasaki disease (KD) is an acute vasculitis of childhood that predominantly affects the coronary arteries. We investigated
single nucleotide polymorphisms (SNPs) of the tryptophan hydroxylase 2 (TPH2) gene as risk factors for KD with coronary artery
lesions (CALs) in Korean children. We genotyped two SNPs [rs7305115 (exon 7) and rs4290270 (exon 9)] using direct sequencing
in 101 KD and 256 control subjects. To analyze the genetic data, SNPStats, SNPAnalyzer, and Helixtree programs were used.
The genotype analysis of rs7305115 and rs4290270 showed no significant differences between KD and control groups. However,
we found a statistically significant association between the two SNPs and the development of CALs in KD (p < 0.05). The minor homozygous genotype (rs7305115, AA genotype and rs42901270, AA genotype) of each SNP showed increased susceptibility
to risk of CALs in KD patients. These results suggest that TPH2 may be associated with the development of KD with CALs in
Korean children.
European Journal of Pediatrics 04/2012; 169(4):457-461. · 1.88 Impact Factor
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ABSTRACT: a disintegrin and metalloproteinase (ADAM) with thrombospondin type 1 motif 12 (ADAMTS12) is a degradative enzyme that interacts with the degradable fragments of cartilage oligomeric matrix protein, which is a prominent non-collagenous matrix component in articular cartilage. ADAMTS12 has been observed in the cartilage, synovial fluid and serum of arthritic patients, and may play an important role in the pathogenesis of arthritis. In the present study, we investigated whether genetic polymorphisms of ADAMTS12 are associated with rheumatoid arthritis (RA). To observe the association between ADAMTS12 and RA, we genotyped three single nucleotide polymorphisms (SNPs) (rs1364044, intron C/T; rs10461703, intron C/T; rs25754, missense Thr1495Ile) of ADAMTS12 using a direct sequencing method in 303 RA patients and 495 control subjects. Multiple logistic regression models were performed to analyze the genetic data. SNPStats and SNPAnalyzer Pro programs were used to estimate the odds ratios, 95% confidence intervals and p-values. Bonferroni's correction (pc) was conducted to obtain a defined result. Of the three SNPs, the genotype frequency of rs10461703 was associated with the development of RA (pc=0.0024 in the co-dominant model; pc=0.0009 in the dominant model; pc=0.0006 in the log-additive model). The allele frequency of rs10461703 also showed a significant difference between RA and controls (pc<0.0001). The C allele frequency of rs10461703 was lower in the RA group (36.6%) compared to the control group (45.7%), whereas the T allele frequency of rs10461703 in the RA group (63.4%) was higher compared to that in the control group (54.3%). The other two SNPs (rs1364044 and rs25754) were not associated with the development of RA. However, we did not find any association between the three tested SNPs and RA patients according to clinical features, including erythrocyte sedimentation rate, C-reactive protein level, rheumatoid factor (+ and -) and bone erosion (+ and -). Our results suggest that ADAMTS12 may be a susceptibility gene for RA development.
Molecular Medicine Reports 04/2012; 6(1):227-31. · 0.42 Impact Factor
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ABSTRACT: We conducted a pilot study to evaluate the effects of pelvic radiotherapy on biologic markers of oxidative stress and plasma endotoxin levels, and to assess the relationship between the changes of such factors and radiotherapy-related complications.
Twelve gynecologic cancer patients who were treated via pelvic radiotherapy with or without concurrent chemotherapy were enrolled in this study. Biologic markers of oxidative stress, such as glutathione (GSH) and oxidized glutathione (GSSG), as well as endotoxin levels, were measured weekly during treatment. Subjective symptoms were assessed using the Korean version of the EORTC QLQ-C30 at the baseline and on the 5th week of radiotherapy.
No changes were noted in the level of GSH in whole blood, but the GSH/GSSG ratio was reduced dramatically after the initiation of radiotherapy. The mean plasma endotoxin for all patients tended to increase and persisted during radiotherapy, and the number of patients who evidenced clinically significant endotoxin levels (defined as >0.005 EU/mL) also increased. Nausea/vomiting and diarrhea were significantly changed (p=0.019 and p<0.001, respectively). A significant relationship was noted to exist between the changes in the endotoxin level and nausea/vomiting (p=0.001). However, such symptoms did not correlate with the changes of oxidative stress markers.
Pelvic radiotherapy oxidized the GSH redox system and increased plasma endotoxin. Further investigations containing interventional and longitudinal studies will be required to assess the effects of the changes in oxidative stress markers and endotoxin on radiotherapy-related adverse events.
Journal of Gynecologic Oncology 04/2012; 23(2):103-9. · 1.49 Impact Factor
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ABSTRACT: Histone modifications and DNA methylation are two major factors in epigenetic phenomenon. Unlike the histone deacetylase inhibitors, which are known to exert radiosensitizing effects, there have only been a few studies thus far concerning the role of DNA methyltransferase (DNMT) inhibitors as radiosensitizers. The principal objective of this study was to evaluate the effects of DNMT inhibitors on the radiosensitivity of human cancer cell lines, and to elucidate the mechanisms relevant to that process.
A549 (lung cancer) and U373MG (glioblastoma) cells were exposed to radiation with or without six DNMT inhibitors (5-azacytidine, 5-aza-2'-deoxycytidine, zebularine, hydralazine, epigallocatechin gallate, and psammaplin A) for 18 hours prior to radiation, after which cell survival was evaluated via clonogenic assays. Cell cycle and apoptosis were analyzed via flow cytometry. Expressions of DNMT1, 3A/3B, and cleaved caspase-3 were detected via Western blotting. Expression of γH2AX, a marker of radiation-induced DNA double-strand break, was examined by immunocytochemistry.
Pretreatment with psammaplin A, 5-aza-2'-deoxycytidine, and zebularine radiosensitized both A549 and U373MG cells. Pretreatment with psammaplin A increased the sub-G1 fraction of A549 cells, as compared to cells exposed to radiation alone. Prolongation of γH2AX expression was observed in the cells treated with DNMT inhibitors prior to radiation as compared with those treated by radiation alone.
Psammaplin A, 5-aza-2'-deoxycytidine, and zebularine induce radiosensitivity in both A549 and U373MG cell lines, and suggest that this effect might be associated with the inhibition of DNA repair.
Radiation Oncology 03/2012; 7:39. · 2.32 Impact Factor
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ABSTRACT: This study was performed to evaluate treatment outcomes and define prognostic factors for primary vaginal cancer treated with definitive radiotherapy.
We retrospectively analyzed 38 patients with primary vaginal cancer who received radiotherapy with curative intent between January 1981 and August 2008. Of these 38 patients, 6 were excluded from this analysis because of other uncontrolled malignancy (n = 1), uncommon histology (n = 4), or insufficient medical records (n = 1). Twenty-three patients (72%) presented with early-stage disease (International Federation of Gynecology and Obstetrics stages 0, I, or II). Eleven patients (34%) were treated with external beam radiotherapy (EBRT) alone and 21 patients (66%) with EBRT plus brachytherapy (BT). Low-dose rate cesium-137 was used with intracavitary technique for most of the patients who received BT. Five patients received chemotherapy. The median total dose in patients who received EBRT and EBRT+BT was 50.4 Gy (range, 39.6-70.4 Gy) and 78.9 Gy (range, 72.0-87.0 Gy), respectively.
The median duration of follow-up was 38 months. Five-year overall survival, cause-specific survival, disease-free survival, local control, and regional control rates for the analyzed patients were 75%, 88%, 58%, 62% and 90%, respectively. Thirteen patients had treatment failure as follows: local (n = 7), distant (n = 1), local plus regional (n = 1), local plus distant (n = 2), and local plus regional plus distant (n = 2). Primary tumor size was a significant prognostic factor for disease-free survival (P = 0.039).
Definitive radiotherapy is an effective treatment modality for primary vaginal cancer. Local failure was the major failure pattern, and achievement of local control is important for disease control and survival.
International Journal of Gynecological Cancer 03/2012; 22(3):521-7. · 1.65 Impact Factor
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ABSTRACT: To compare the long-term clinical outcomes of adjuvant radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT) in cervical cancer patients with intermediate risk factors.
Between 1990 and 2010, 110 cervical cancer patients with 2 or more intermediate risk factors (deep stromal invasion, lymphovascular space invasion, and large tumor size) underwent adjuvant RT (n=56) or CCRT (n=54) following radical surgery. Because CCRT had been performed since 2000, patients were divided into 3 groups regarding treatment period and the addition of chemotherapy, RT 1990-1999 (n=39), RT 2000-2010 (n=17) and CCRT 2000-2010 (n=54). Majority of concurrent chemotherapeutic regimens were carboplatin and paclitaxel (n=48).
Five-year relapse-free survival (RFS) rates for RT 1990-1999, RT 2000-2010 and CCRT 2000-2010 were 83.5%, 85.6% and 93.8%, respectively. CCRT 2000-2010 had a significant decrease in pelvic recurrence (p=0.012) and distant metastasis (p=0.027). There were no significant differences in overall survival and RFS between RT 1990-1999 and RT 2000-2010. Acute grade 3 and 4 hematologic toxicities were more frequently observed in CCRT 2000-2010 (p<0.001). However, acute grade 3 and 4 gastrointestinal (GI) and chronic toxicities did not differ between the groups.
This study shows that the addition of concurrent chemotherapy to postoperative RT in cervical cancer patients with intermediate risk factors may improve RFS without increasing acute GI and chronic toxicities, although hematologic toxicities increased significantly.
Gynecologic Oncology 01/2012; 124(1):63-7. · 3.89 Impact Factor
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ABSTRACT: Insulin-like growth factor 1 (IFG1) is neuroprotective in animal models of focal brain ischemia and correlates with ischemic stroke (IS) outcome in the elderly. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of the IFG1 gene are associated with the development and clinical features of IS in a Korean population. A total of 119 patients with IS and 289 control subjects were recruited. Stroke patients were classified into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS; <6 and ≥6) and the Modified Barthel Index (MBI; <60 and ≥60). Among the SNPs of the IFG1 gene, five SNPs were selected and analyzed by direct sequencing: rs2162679 (intron), rs2195239 (intron), rs978458 (intron), rs1520220 (intron) and rs6214 (3' untranslated region; 3'UTR). Multiple logistic regression models were conducted to analyze genetic data. SNPStats, SNPAnalyzer Pro and Helixtree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and p-values. Two SNPs, rs2162679 and rs6214, were associated with the development of IS. After Bonferroni correction (p(c)), the A and G alleles of rs2162679 and rs6214 had significant differences between patients with IS and the controls [rs2162679, OR (95% CI) = 1.64 (1.17-2.31), p=0.004, p(c)=0.02; rs6214, OR (95% CI) = 1.52 (1.12-2.07), p=0.007, p(c)=0.035], respectively. However, the five selected SNPs were not related to the NIHSS and MBI scores. These results suggest that IGF1 may be associated with the development of IS.
Experimental and therapeutic medicine 01/2012; 3(1):93-98.
