Cancer Research and Treatment

The Effect of Pentoxifylline on Radiobiological Parameters in the Rat Radiation Myelopathy: Won Dong Kim, Woo Yoon Park; Cancer Res Treat. 2006;38(4):229-233. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.229

Abstract PDF PubReader ePub: Purpose
There is great recent interest in the potential value of using pentoxifylline (3,7-dimethyl-1(5-oxyhexyl)-xanthine, PTX) as an inhibitor of radiation-induced late normal tissue damage. The effects of PTX on the radiobiological parameters (α/β ratio, repair half time T_1/2) of radiation myelopathy were studied in a rat model.
Materials and Methods
Anesthetized Sprague-Dawley rats received irradiation to 2 cm of their cervical spines with using a 6MV LINAC (dose rate: 3 Gy/min). Radiation was administered in single, two, four and eight fractions with a fraction interval of 24 h with or without PTX. PTX was added to the rats' distilled drinking water at a concentration of 2 g/L; the water was consumed ad libitum. After tabulation of the ED₅₀ (the estimated dose needed to produce 50% paralysis in a group of irradiated animals), α/β could be estimated from the ratio of the slope to the intercept of the reciprocal-dose plot. Subsequently, the repair half time T_1/2 was obtained from the data of the experimental group that received a pair of 7 Gy fractions on each day, separated by intervals of 4 and 8 h.
Results
The α values calculated for RT alone and RT+ PTX were almost the same. We noticed that the β value for the RT+PTX was lower than that for RT alone. So, the α/β ratio for the RT+PTX was higher. The T_1/2 obtained from monoexponential model was 3.27 and 2.58 h for RT alone and RT+PTX, respectively.
Conclusion
PTX increased the α/β ratio and it decreased the T_1/2 of radiation myelopathy, suggesting that a decreasing fractionation sensitivity occurred. This implies that PTX, which distinctly acts upon the bending region of the high dose, may be expected to protect the spinal cord with a larger fraction size.

7,533 View
40 Download

The Combined Effects of Amifostine and Interleukin 1 Beta (IL-1beta) on Radiation-induced Gastrointestinal and Hematopoietic Injury: Seong Soon Jang, Woo Yoon Park; Cancer Res Treat. 2003;35(6):528-532. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.528

Abstract PDF: PURPOSE
The pattern of radioprotection by the combined use of low dose amifostine plus IL-1beta was investigated in mice exposed to an acute whole-body radiation dose of 10 Gy.
MATERIALS AND METHODS
Male ICR mice were divided into the control group, the irradiation-only group, the high dose amifostine (400 mg/kg i.p. 30 min before irradiation) group, and the low dose amifostine (200 mg/kg i.p. 30 min before irradiation) plus IL-1beta (5 microgram/kg i.p. 20 h before irradiation) group. The radioprotective effects were evaluated using TUNEL assay and microcolony survival assay at jejunal crypt, bone marrow cell count and CBC in peripheral blood, and survival analysis up to 30 days following irradiation. RESULTS: The apoptotic index (p=0.987), surviving crypt number (p=0.484), and the number of WBCs (p=0.226), RBCs (p=0.544), and platelets (p=0.157) were not significantly different between the high dose amifostine group and the low dose amifostine plus IL-1beta group, although the bone marrow cell count was higher in the combination group. The irradiation-only group was dead within 15 days. However, the survival rate at 30 days in the high dose amifostine and the low dose amifostine plus IL-1beta pretreatments were 61% and 66%, respectively. Moreover, the differences between the two groups were insignificant for both 10 days (p=0.9461) and 30 days (p=0.8030). CONCLUSION: These results indicate that the low dose amifostine plus IL-1beta may be applied as a non-toxic radioprotector, while the high dose amifostine, known as the strongest radioprotector, however, had toxic side effects.

3,173 View
21 Download

Concurrent FP (5-fluorouracil, cisplatin) Chemoradiotherapy for Patients with Esophageal Cancer: Min Ok Kim, Eui Sil Hong, Ji Young Chai, Joung Muk Leem, Il Young You, Won Dong Kim, Woo Yoon Park, Seung Taik Kim, Ki Hyeong Lee; Cancer Res Treat. 2003;35(4):330-334. Published online August 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.4.330

PURPOSE
The outcomes of a surgical approach for patients with an esophageal carcinoma remain unsatisfactory despite its high complication rates. We conducted a phase II trial, using combined FP (5-fluorouracil and cisplatin) chemotherapy and concurrent radiotherapy, as a definitive therapy for patients with esophageal cancer.
MATERIALS AND METHODS
Patients with histologically proven esophageal cancer were enrolled onto this study. The treatment consisted of four courses of chemotherapy and six and a half weeks of radiotherapy. The patients received chemotherapy in weeks 1, 5, 12 and 16 (5-fluorouracil 1, 000 mg/m2 on days 1 to 4 and cisplatin 75 mg/m2 on day 1). Radiotherapy was administered at a dose of 59.4 Gy, in five 1.8 Gy fractions a week.
RESULTS
A total of 22 eligible patients entered the study. Of the 19 evaluable patients, a complete response occurred in 7 (37%), and a partial response in 8 (42%). After a median follow-up of 35 months, the overall survival rate was 32% at three years and the median survival was 11 months. Fourteen (64%) received planned dose of radio-therapy and 13 (59%) received more than three courses of chemotherapy. However, there was no difference in three-year survival rates between the patients that received less than three courses of chemotherapy and those that received three or more courses (31% vs. 32%). The major treatment related toxicity was mucositis, which developed in every patient, with grades III or IV in thirteen (59%) patients. During the treatment, the patients lost, on average, 3.8% of their body weight. The mean hospital stay was 23 days, with a total duration of treatment of 74 days.
CONCLUSIONS
Concurrent FP chemoradiotherapy was effective as a definitive therapy for patients with esophageal cancer. The major toxicity was mucositis. Although the treatment was relatively feasible, a randomized trial of reduced courses of chemotherapy is warranted.

Citations

Citations to this article as recorded by

Anti-cancer Effects of a Novel Quinoline Derivative 83b1 on Human Esophageal Squamous Cell Carcinoma through Down-Regulation of COX-2 mRNA and PGE₂
Ivan Ho Yuen Pun, Dessy Chan, Sau Hing Chan, Po Yee Chung, Yuan Yuan Zhou, Simon Law, Alfred King Yin Lam, Chung Hin Chui, Albert Sun Chi Chan, Kim Hung Lam, Johnny Cheuk On Tang
Cancer Research and Treatment.2017; 49(1): 219. CrossRef
Bi-weekly Chemotherapy of Paclitaxel and Cisplatin in Patients with Metastatic or Recurrent Esophageal Cancer
Sang-Hee Cho, Ik-Joo Chung, Sang-Yun Song, Deok-Hwan Yang, Jeong-Rae Byun, Yeo-Kyeoung Kim, Je-Jung Lee, Kook-Joo Na, Hyeoung-Joon Kim
Journal of Korean Medical Science.2005; 20(4): 618. CrossRef

4,842 View
30 Download
2 Crossref

5-Fluorouracil and Cisplatin (FP) with Concurrent Radiotherapy for Locally Advanced Head and Neck Cancer: Hyoung Sam Kim, Ki Seok Kim, Sang Seok Bea, Seok Jin Oh, Ki Hyeong Lee, Won Dong Kim, Woo Yoon Park, Seung Taik Kim; Cancer Res Treat. 2002;34(4):296-301. Published online August 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.4.296

Abstract PDF

The combination of chemotherapy and radiotherapy is emerging as the new standard modality for the treatment of locally advanced head and neck cancer, due to the inherent functional and cosmetic sequelae associated with its surgical management. Combination chemotherapy with 5-fluorouracil and cisplatin (FP) is one of the most active regimens for the head and neck cancer. Furthermore, both agents are known to act as radiosensitizer. This study was conducted to determine the efficacy, feasibility, and the toxicities of concurrent FP chemotherapy with radiotherapy.
MATERIALS AND METHODS
Patients with histologically proven locally advanced head and neck cancer (T3-4 or node positive) were enrolled in the study. Patients received 5-fluorouracil, 1,000 mg/m2/day, continuously for 4 days, and cisplatin, 75 mg/m2, on day 1. This regimen was given every four weeks. The radiotherapy (45 Gy) was started on day 1 of the first cycle, and administered in 25 fractions. Following a three-week interval, the radiotherapy was resumed on day 1 of the third cycle of chemotherapy, and administered in 15 fractions (27 Gy).
RESULTS
Of the 31 eligible patients included, 28 were able to be evaluated for the tumor response. The response rate for the 28 patients was 93% (16 complete responses, 10 partial responses). Disease free survival for the 16 complete responders was 37 months (median, 1 ~41 months), with a median follow-up time of 31 months. The 1-, 2-, and 3-year survival rates were 82%, 69%, and 63%, respectively. Regarding the feasibility of this treatments, only nineteen patients (61%) received the complete courses of scheduled treatments. The median duration of admission for all patients was 39 days. Grade 3 or 4 stomatitis were observed in 25 patients (83%) and appeared as the dose limiting toxicity of this regimen CONCLUSION: Although FP chemotherapy with concurrent radiotherapy is toxic, it is an effective and relatively feasible treatment for locally advanced head and neck cancer. The majority of patients experienced severe stomatitis, which appeared as the dose limiting toxicity of this regimen.

Citations

Citations to this article as recorded by

Chemotherapy of Head and Neck Cancer
Chang Ki Yeo
Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2014; 57(5): 291. CrossRef

4,977 View
32 Download
1 Crossref

Nausea and Vomiting Induced by Conventional Fractionated Radiotherapy on Abdomen: Won Dong Kim, Woo Yoon Park; J Korean Cancer Assoc. 2000;32(4):757-763.

Abstract PDF: PURPOSE
A retrospective study was intended to assess the incidence, severity, and risk factors of abdominal radiotherapy induced nausea and vomiting and to evaluate the effect of antiemetic drugs like metoclopramide and ondansetron.
MATERIALS AND METHODS
From October 1997 to October 1999, we enrolled 48 patients who received conventional fractionated radiotherapy on abdomen. Patients under 18 years old and who received concomittant chemotherapy were excluded. Evaluation was carried out on the basis of daily check of the intensity of nausea and any episode of vomiting and retching.
RESULTS
Nausea and vomiting occurred in 65% and 25% of patients, respectively. On multivariate analysis, previous experience with chemotherapy was the only significant patients-related risk factor. The irradiated site and field size were also significant in terms of radiotherapy-related risk factors. Nausea and vomiting were markedly diminished in the group given ondansetron.
CONCLUSION
Our study offered useful data on general picture of radiation induced nausea and vomiting in patients given conventional fractionated radiotherapy on abdomen. For the patients with risk factors, prophylactic antiemetic drug prescription may be mandatory to enhance compliance with radiotherapy and ondansetron is more effective than metoclopramide for controlling nausea and vomiting.

2,163 View
17 Download

Radiosensitivity in Acquired Cisplatin-Resistant Human Stomach Adenocarcinoma Cells: Woo Yoon Park, Weon Seon Hong; J Korean Cancer Assoc. 1997;29(4):584-589.

Abstract PDF: No abstract available

2,336 View
14 Download

Palliative Radiotherapy for Painful Bone Metastases: Won Dong Kim, Woo Yoon Park; J Korean Cancer Assoc. 1997;29(2):250-256.

Abstract PDF: No abstract available

2,212 View
12 Download

Expression of cellular Oncogenes During the Radiation - induced Leukemogenesis in CBA Mice: Woo Yoon Park, Jeong Sun Seo; J Korean Cancer Assoc. 1990;22(3):410-424.

Abstract PDF: To explore whether the development of the specific tumor type in experimental animal model for the study of radiation-induced carcinogenesis is caused by genetic predisposition, such as species or strain, or irradiation method, and also to find out the role of cellular oncogenes in radiation-induced carcinogenesis, an experimental study was made using female CBA mice. After total 450 cGy of whole-body irradiation with 3 fractionations at weekly intervals, histopathologic changes and expression of cellular oncogenes were examined with thymus and bone marrow serially till postirradiation 150 days in 18 female CBA mice. Simultaneously unirradiated 12 mice were studied as a control. The results are as follows. 1) Thymic lymphoma/leukemia did not develop in CBA mice with the fractionated whole-body irradiation which has been known to be an effective method af inducing thymic lymphorna/leukemia in C57BL mice. Increment of blasts in bone marrow, which suggests the development of myeloid leukemia, was observed in 33%(2/6) of irradiated mice elapsed 150 days after irradiation. These findings suggest that the development of the specific tumor type in experimental animal is not related to irradiation method but to genetic predisposition, such as differences in species or strain. 2) The expressian of two cellular oncogenes, c-fps and c-myc, as a parameter of chemical changes were examined at thymus serially till postirradiation 150 days. No abnormal expression of c-fps or c-myc was observed as with the findings of histopathology. 3) In the examination of two cellular oncogenes in bone marrow, there was no change in c-myc, but there was strong expression of c-fps in one of mice elapsed 150days after irradiation. The expression of c-fps at preleukemic state suggests that the chemical changes develop before the appearance of malignancy as a phenotype. This result is very meaningful in that specific oncogenes might play a role in radiation-induced carcinogenesis.

2,348 View
14 Download

The Effect of Hydralazine on Hyperthermic Treatment of C3H Mouse Fibrosarcoma: Woo Yoon Park, Sung Whan Ha, Charn Il Park; J Korean Cancer Assoc. 1995;27(4):671-680.

Abstract PDF: Hypoxic cells comprise l0~20% of tumor cells and are more sensitive to hyperthermia. By decreasing tumor blood flow artificially and thus increasing the hypoxic fraction in the tumor, the cytotoxic effect of hyperthermia can be increased. Hydralazine is an antihypertensive drug and its main mechanism is relaxation of the vascular smooth muscle of arterioles rather than veins. Administration of hydralazine causes a decrease in vascular resistance and an increase in blood flow in normal tissue, but since the vasculature of tumor is not responsive to such a drug, blood flow in tumors is decreased because of steal phenomenon. Thus the hypoxic fraction in the tumor is increased, and the tumor becomes more sensitive to hyperthermia. Therefore, to evaluate the hydralazine effect on hyperthermia, the tumor growth delay was investigated and the change in the hynoxic fraction of the tumor was estimated using C3H mouse fibrosarcoma(FSaII) with hypoxic fractions af usual range. In 6 mm FSaII tumors grow- ing in the dorsum of the foot, administration af 5 or l0 mg/kg of hydralazine was followed by 43`C, hyperthermia for 60 minutes. Tumor growth times (TGT) to reach a tumor volume of 500 mm(2) were 7.11+-0.84 days and 7.44+- 1.13 days for controls and 10 mg/kg of hydralazine only. TGTs for hyperthermia alone and administration of 5 or 10 mg/kg of hydralazine followed by hyperthermia were 10.34+-2.17 days, 13.38+-1.82 days and 14.47+- 0.67 days, respectively. Elongation of tumor growth delay by administration of 5 or l0 mg/kg of hydralazine in addition to hyperthermia were statistically significant (0.025

2,511 View
13 Download

Search