• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.825-830
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• 2014

Objective: The purpose of this study was to examine the role of programmed cell death 4 (PDCD4) expression in predicting tumor response to neoadjuvant chemoradiotherapy and outcomes for patients with locally advanced rectal cancer. Methods: Clinicopathological factors and expression of PDCD4 were evaluated in 92 patients with LARC treated with nCRT. After the completion of therapy, 4 cases achieved clinical complete response (cCR), and thus the remaining 88 patients underwent a standardized total mesorectal excision procedure. There were 38 patients (41.3%) with a good response (TRG 3-4) and 54 (58.7%) with a poor one (TRG 0-2). Results: Immunohistochemical staining analyses showed that patients with high expression of PDCD4 were more sensitive to nCRT than those with low PDCD4 expression (P=0.02). High PDCD4 expression before nCRT and good response (TRG3-4) were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis demonstrated that the pretreatment PDCD4 expression was an independent prognostic factor. Conclusion: Our study demonstrated that high expression of PDCD4 protein is a useful predictive factor for good tumor response to nCRT and good outcomes in patients with LARC.

• Radiation Oncology Journal
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• 제37권2호
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• pp.117-126
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• 2019

Purpose: The purpose of this study was to characterize and evaluate the clinical significance of volume changes of soft tissue sarcomas during radiation therapy (RT), prior to definitive surgical resection. Materials and Methods: Patients with extremity or pelvis soft tissue sarcomas treated at our institution from 2013 to 2016 with RT prior to resection were identified retrospectively. Tumor volumes were measured using cone-beam computed tomography obtained daily during RT. Linear regression evaluated the linearity of volume changes. Kruskal-Wallis tests, Mann-Whitney U tests, and linear regression evaluated predictors of volume change. Logistic and Cox regression evaluated volume change as a predictor of resection margin status, histologic treatment response, and tumor recurrence. Results: Thirty-three patients were evaluated. Twenty-nine tumors were high grade. Prior to RT, median tumor volume was 189 mL (range, 7.2 to 4,885 mL). Sixteen tumors demonstrated significant linear volume changes during RT. Of these, 5 tumors increased and 11 decreased in volume. Myxoid liposarcoma (n = 5, 15%) predicted decreasing tumor volume (p = 0.0002). Sequential chemoradiation (n = 4, 12%) predicted increasing tumor volume (p = 0.008) and corresponded to longer times from diagnosis to RT (p = 0.01). Resection margins were positive in three cases. Five patients experienced local recurrence, and 7 experienced distant recurrence, at median 8.9 and 6.9 months post-resection, respectively. Volume changes did not predict resection margin status, local recurrence, or distant recurrence. Conclusion: Volume changes of pelvis and extremity soft tissue sarcomas followed linear trends during RT. Volume changes reflected histologic subtype and treatment characteristics but did not predict margin status or recurrence after resection.

• Environmental Analysis Health and Toxicology
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• 제31권
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• pp.1.1-1.13
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• 2016

Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (A-bomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down's syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about linear dose response.

• Radiation Oncology Journal
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• 제32권1호
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• pp.31-42
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• 2014

Purpose: To evaluate the usefulness of positron emission tomography/computed tomography (PET/CT) for field modification during radiotherapy in esophageal cancer. Materials and Methods: We conducted a retrospective study on 33 patients that underwent chemoradiotherapy (CRT). Pathologic findings were squamous cell carcinoma in 32 patients and adenocarcinoma in 1 patient. All patients underwent PET/CT scans before and during CRT (after receiving 40 Gy and before a 20 Gy boost dose). Response evaluation was determined by PET/CT using metabolic tumor volume (MTV), total glycolytic activity (TGA), MTV ratio (rMTV) and TGA ratio (rTGA), or determined by CT. rMTV and rTGA were reduction ratio of MTV and TGA between before and during CRT, respectively. Results: Significant decreases in MTV ($MTV_{2.5}$: mean 70.09%, p < 0.001) and TGA ($TGAV_{2.5}$: mean 79.08%, p < 0.001) were found between before and during CRT. Median $rMTV_{2.5}$ was 0.299 (range, 0 to 0.98) and median $rTGAV_{2.5}$ was 0.209 (range, 0 to 0.92). During CRT, PET/CT detected newly developed distant metastasis in 1 patient, and this resulted in a treatment strategy change. At a median 4 months (range, 0 to 12 months) after completion of CRT, 8 patients (24.2%) achieved clinically complete response, 11 (33.3%) partial response, 5 (15.2%) stable disease, and 9 (27.3%) disease progression. $SUV_{max}$ (p = 0.029), $rMTV_{50%}$ (p = 0.016), $rMTV_{75%}$ (p = 0.023) on intra-treatment PET were found to correlate with complete clinical response. Conclusion: PET/CT during CRT can provide additional information useful for radiotherapy planning and offer the potential for tumor response evaluation during CRT. $rMTV_{50%}$ during CRT was found to be a useful predictor of clinical response.

• 대한두경부종양학회지
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• 제22권2호
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• pp.123-129
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• 2006

Objective ： This retrospective study was designed to evaluate the anti-tumor efficacy and toxicities of the radiation therapy(RT) combined with cisplatin-based chemotherapy in locally advanced nasopharyngeal cancer(NPC). Materials and Methods ： Fifty three patients with locally advanced NPCs(AJCC stage II, III, IV) received curative RT and cisplatin-based chemotherapy. Duration of follow-up ranged from 5.5 to 201 months(median 50.8 months). Nineteen patients(35.8%) were treated with induction chemotherapy including cisplatin $100mg/m^2$ for 1 day and 5-fluorouracil $1g/m^2$ for 5 days followed by RT(Induction CTx-RT). Another 34 patients (64.2%) were treated with concurrent chemoradiation(CCRT) using cisplatin $100mg/m^2$(D1, 22, 43). Results ： Thirty-six(67.9%) and 11(20.8%) patients achieved clinical complete response and partial response, respectively. The pattern of failure was as follows：14 locoregional recurrence(26.4%) and 7 distant metastasis(13.2%). Among them, two patients(3.8%) had both locoregional and distant failure. Median overall survival(OS) and progression-free survival(PFS) were 85.5 months and 87.5 months, respectively. Five-year OS rate was 57.1%. The stage(AJCC), tumor response to chemoradiation and T stage were significant prognostic factors for OS(p=0.0113, p=0.0362 and p=0.0469). The stage(AJCC), tumor response to chemoradiation were also significant prognostic factors for PFS(p=0.0329, p=0.0424). Compared to each treatment group(Induction CTx-RT vs. CCRT), there were no significant differences in OS and PFS(p=0.7000, p=0.8261). Grade 3-4 mucositis, nausea/vomiting and hematological toxicities were noticed in 35.8%, 11.3% and 13.2%, respectively. Delayed RT over 2 weeks was inevitable in 26.5%. Seventeen patients(50%) successfully completed planned 3 courses of cisplatin in CCRT group. Conclusions ： RT combined with cisplatin-based chemotherapy in locally advanced NPC showed high response rate, good locoregional control, and survival rate. As expected, frequency of acute toxicities increased, and the patient's compliance to treatment was need to be improved. Although our data could not show additional survival benefit of CCRT compare to that of induction chemotherapy followed by RT, patients' accrual and further follow-up are required due to limitation of retrospective study.

• Journal of Microbiology and Biotechnology
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• 제23권12호
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• pp.1785-1790
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• 2013

The synthetic machinery of ATF4 (activating transcription factor 4) is activated in response to various stress conditions involved in nutrient restriction, endoplasmic reticulum homeostasis, and oxidation. Stress-induced inhibition of proteasome activity triggers the unfolded protein response and endoplasmic reticulum stress, where ATF4 is crucial for consequent biological events. In the current study, we showed that the $NAD^+$-dependent deacetylase, SIRT1, suppresses ATF4 synthesis during proteasome inhibition. SIRT1 depletion via transfection of specific siRNA into HeLa cells resulted in a significant increase in ATF4 protein, which was observed specifically in the presence of the proteasome inhibitor MG132. Consistent with SIRT1 depletion data, transient transfection of cells with SIRT1-overexpressing plasmid induced a decrease in the ATF4 protein level in the presence of MG132. Interestingly, however, ATF4 mRNA was not affected by SIRT1, even in the presence of MG132, indicating that SIRT1-induced suppression of ATF4 synthesis occurs under post-transcriptional control. Accordingly, we propose that SIRT1 serves as a negative regulator of ATF4 protein synthesis at the post-transcriptional level, which is observed during stress conditions, such as proteasome inhibition.

• Radiation Oncology Journal
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• 제13권1호
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• pp.55-61
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• 1995

Purpose : Despite a development of therapeutic machines and advance in modern radiation therapy techniques, locally advanced cervical carcinoma has shown high rate of local failure and poor survival rate, Combination of chemotherapy and radiotherapy demonstrated benefit in improving local control and possibly the overall survival. Our study was performed to evaluate effect of concurrent chemoradiation on locally advanced uterine cervical cancer. Methods and Materials : Twenty six patients with locally advanced stage(FIGO stage IIB with ${\geq}5cm$ in diameter, III, IVA) were treated with combination of radiation therapy and concurrent cisplatinum between May of 1988 and September of 1993 at our hospital. Radiation therapy consisted of external irradiaton and 1-2 sessions of intracavitary irradiation. Cisplatinum was administered in bolus injection of 25mg/$m^2$ at weekly intervals during the course of external radiation therapy. Results : Of the 26 Patients, twenty-five patients were evaluable for estimation of response. Median follow-up period was 25 months with ranges from 3 to 73 months. Stage IIB, III, and IVA were 16, 5, 4 patients, respectively, Twenty patients were squamous cell carcinoma. Response was noted in all 25 patients: complete response(CR) in 17/25($68\%$), Partial response(PR) in 8/25($32\%$). Of the 24 patients except one who died of sepsis at 3 months follow-up, seventeen patients($70.8\%$) maintained local control in the pelvis: 16/17($94.1\%$) in CR, 1/17($14.3\%$) in PR. Fourteen of the 17 patients with CR are alive disease free on the completion of follow-up. Median survival is 28 months for CR and 15 months for PR. Analysis of 5-year survival by stage shows 11/16($59.8\%$) in IIB, 3/5($60.0\%$) in III, and 1/4($25.0\%$) in IVA. Overall 5-year survival rate was $55.2\%$. Ten patients recurred: 4 at locoregional, 3 in distant metastasis and 3 with locoregional and distant site. Toxicity by addition of cisplatinum was not excessive. Conclusion : Although the result of this study was obtained from small number of patients, it is rather encouraging in view of markedly improved response rate compared with the results of historical group.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2477-2481
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• 2013

Aims and Background: The purpose of the research was to study the prognostic value of tumor 18F-FDG PET-based parameters in neoadjuvant chemoradiation for patients with squamous esophageal carcinoma. Methods: Sixty patients received chemoradiation therapy followed by esophagectomy and two 18FDG-PET examinations at pre- and post-radiation therapy. PET-based metabolic-response parameters were calculated based on histopathologic response. Linear regression correlation and Cox proportional hazards models were used to determine prognostic value of all PET-based parameters with reference to overall survival. Results: Sensitivity (88.2%) and specificity (86.5%) of a percentage decrease of SUVmax were better than other PET-based parameters for prediction of histopathologic response. Only percentage decrease of SUVmax and tumor length correlated with overall survival time (linear regression coefficient ${\beta}$: 0.704 and 0.684, P<0.05). The Cox proportional hazards model indicated higher hazard ratio (HR=0.897, P=0.002) with decrease of SUVmax compared with decrease of tumor size (HR=0.813, P=0.009). Conclusion: Decrease of SUVmax and tumor size are significant prognostic factors in chemoradiation of esophageal carcinoma.

• Radiation Oncology Journal
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• 제37권4호
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• pp.302-308
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• 2019

The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain's distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient's tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms of headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient's CNS metastases improved significantly within weeks of her therapy. The patient's non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.

• Journal of Microbiology and Biotechnology
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• 제11권3호
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• pp.524-528
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• 2001

The measurement of radiation response using simple and informative techniques would be of great value in studying the genetic risk following occupational, therapeutic, or accidental exposure to radiation. When patients receive radiation therapy, many suffer from side effects. Since each patient receives a different dose due to different physical conditions, it is important to measure the exact dose of radiation received by each patient to lessen the side effects. Even though several biological dosimetric systems have already been developed, there is no ideal system that can satisfy all the criteria for an idean dosimetric system, especially for low-dose radiation as used in radiation therapy. In this study, an SOS Chromotest of E. coli PQ37 was evaluated as a novel dosimeter for low-dose gamma-rays. E. coli PQ37 was originally developed to screen chemical mutagens using the SOS Chromotest-a colorimtric assay, based on the induction of ${\beta}$-galactosidase ue to DNA damage. The survival fraction of E. coli PQ37 decreased dose-dependently with an increasing dose of cobalt-60 gamma-rays. Also, a good linear correlation was found between the biological damage revealed by the ${\beta}$-galactosidase expression and the doses of gamma-rays. The expression of ${\beta}$-galactosidase activity that responded to low-dose radiation under 1 Gy was $Y=0.404+(0.089{\pm}0.3)D+(-0.018{\pm}0.16)D^2$ (Y, absorbance at 420 nm; D, Dose of irradiation) as calculated using Graph Pad In Plot and Excel. When a rabbit was fed with capsules containing an agar block embdded with E. coli PQ37 showed a linear response to the radiation doses. Accordingly, the results confirm that E. coli PQ37 can be used as a sensitive biological dosimeter fro cobalt-60 gamma-rays. To the best of our knowledge, this is the first time that a bacterium has been used as a biological dosimeter, especially for low-dose radiation.