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The CD36 dynamic change after radiation therapy in lung cancer patients and its correlation with symptomatic radiation pneumonitis
Radiotherapy and Oncology 107 (2013) 389–391
Contents lists available at SciVerse ScienceDirect
Radiotherapy and Oncology journal homepage: www.thegreenjournal.com
Morbidity of lung cancer RT
The CD36 dynamic change after radiation therapy in lung cancer patients and its correlation with symptomatic radiation pneumonitis Lu Bai b, Junhua Zhao c, Hong Yu d, Na Zhao a, Dan Liu a, Wen Zhong a, Yuxia Zhao a,⇑ a
Department of Radiation Oncology, Fourth Affiliated Hospital of China Medical University; b Department of Radiation Oncology, First Affiliated Hospital of China Medical University; c Department of the Seven-year clinics of China Medical University; d Department of Radiation Oncology, Liaoning Cancer and Institute, People’s Republic of China
a r t i c l e
i n f o
Article history: Received 22 February 2012 Received in revised form 28 March 2013 Accepted 14 April 2013 Available online 14 May 2013
a b s t r a c t This study was carried out to investigate the relationship between serum CD36 levels and radiation pneumonitis in 30 patients irradiated for lung cancer. We found CD36 may become an important index for predicting the occurrence and development of radiation pneumonitis and evaluating the curative effect. Ó 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 107 (2013) 389–391
Keywords: Radiation-induced pneumonitis Lung cancer CD36 Radiotherapy
Radiation-induced inflammation plays a critical role in normal tissue response. Normal tissue injury involves complex interactions, including damage to parenchymal cells, vasculature, endothelial cells, stroma and interactions with and response of the tissue micro-environment, particularly the effects of inflammatory cytokines [1,2]. Thoracic radiotherapy is limited by the high radiosensitivity of the normal lung parenchyma [3,4]. It was reported that the clinically significant radiation lung injury occurred in up to 30% of patients irradiated for lung cancer [5] and about 10– 15% of other thoracic oncology patients [6]. Besides, a larger proportion of patients will have subclinical adverse effects of radiation on the lung, which can be identified by imaging and/or physiologic testing [7]. There are two types of radiation lung injury. Acute radiation pneumonopathy (pneumonitis) can occur several weeks to six months post-irradiation with cough, shortness of breath, fever and changes in pulmonary function. The second type of radiation – induced lung injury is referred to the ‘‘fibrotic’’ phase months to years after irradiation. Although the pathogenesis of RP remains unclear, several studies have reported that a variety of cytokines, chemokines, were involved in [8–10] the inflammatory process of RP. Transforming growth factorb-1 (TGFb-1) had been [11,12] identified playing a critical role in the occurrence and development of lung fibrosis. The activation of TGFb-1 needs the regulation by CD36. CD36 could regulate the production of collagen by the way ⇑ Corresponding author. Address: Department of radiation oncology, The fourth affiliated hospital of China Medical University, No. 4, Eastern Chongshan Road, Huanggu District, Shenyang 110032, People’s Republic of China. E-mail address: [email protected] (Y. Zhao). 0167-8140/$ - see front matter Ó 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.radonc.2013.04.014
of acting on the pro-fibrogenic pathway of TGF-b1. In the lung fibrosis module of bleomycin-induced rat, the activated TGF-b1 (released by alveolar macrophage) decreased when the rat was administered CD36 antibody and the synthesis of inflammation and connective tissue also decreased [13]. However, there is no report on the relationship between serum CD36 level and radiationinduced pneumonitis. Whether CD36 could become a reliable predictor for radiation-induced pneumonitis?
Material and methods Patients The case group included 30 RP patients with lung cancer after thoracic three dimensional conformal radiotherapy from December 2008 to May 2011. The control group was established from 30 patients with lung cancer without RP after radiation by case– control study with frequency matched principle. All participants were recruited at the first affiliated hospital of China Medical University and Liaoning Cancer Hospital and Institute. All patients presented with histologically or cytologically confirmed lung cancer, with no history of pulmonary radiotherapy, a Karnofsky performance status of >60, and an expected survival of >6 months. The exclusion criteria included pneumonectomy, severe cardiopulmonary disease and diabetes. This study was approved and supported by the institutional review board of the first affiliated hospital of China Medical University. Written, informed consent was obtained from each patient for the use of blood and clinical data. It was a retrospective study.
390
The CD36 dynamic change in patients with radiation pneumonitis
Table 1 Scoring criteria for evaluation after steroid treatment. Responding to steroid
Table 2 CD36 levels in RP group and control group (pg/ml). Not responding to steroid
Symptom
Improved
CT image
Contracted 0.5 times or more than that was diagnosed
RP group CD36 levels
No change or more serious No change or evolved
a b
28.07 ± 4.80
Control group a
17.09 ± 1.95
b
P value <0.05
Onset of RP diagnosis. 3 Months after radiotherapy.
Table 3 Change of serum CD36 levels during different time points (pg/ml).
Evaluation of RP Physical examination and computed tomography (CT) were performed at the onset of RP, 1 month and 3 months after diagnosis. Common Terminology Criteria for Adverse Events version 3.0 were used to grade RP, as follows: grade 0, no change; grade 1, asymptomatic radiographic findings only; grade 2, symptomatic, not interfering with activities of daily living; grade 3, symptomatic, interfering with activities of daily living, O2 therapy required; grade 4, life-threatening ventilatory support required; and grade 5, severe pneumonitis resulting in death. The evaluation was accomplished by two veteran radiologists together. Patients with RP P Grade 2 were selected for our research. Grade 1 RP was not included in our study.
Therapeutic strategy and evaluation after treatment The patients with radiation pneumonitis (RP) were diagnosed when they come to hospital with respiratory symptoms. ‘‘1 month and 3 month after diagnosis of RP’’ refers to the evaluation time points of treatment effect by methylprednisolone. All RP patients in the case group received methylprednisolone therapy after diag-
Onset of RP 1 Month after diagnosis 3 Months after diagnosis
Total group
Responding to steroid
Not responding to steroid
27.67 ± 3.40 23.99 ± 8.93*
27.35 ± 1.25 18.61 ± 1.58
28.49 ± 5.75 33.68 ± 8.49**
20.88 ± 8.58*
15.44 ± 1.42
30.66 ± 7.17**
*
P < 0.05, CD36 levels decreased significantly by steroid treatment after diagnosis. P < 0.05, CD36 levels decreased significantly in patients responding to steroid, while not shown in patients not responding to steroid.
**
nosis. The original dosage was 32 mg once a day, with 8 mg decreased weekly for 4 weeks. There were two time points for the effect evaluation by steroid treatment: 1 month and 3 months after diagnosis. The treatment effect was evaluated according to the improvement of clinical symptom, CT image and pulmonary function. The evaluation criteria were divided into responding to steroid (symptom improved with cough or dyspnea release, temperature decrease, the moist rale reduce or disappear; The patchy shadow or obscured-glass shadow on CT image contracted
(a) when diagnosis
(b) 1 month after diagnosis
Fig. 1. CT images of a RP patient during diagnosis (a) and 1 month after diagnosis (b).
L. Bai et al. / Radiotherapy and Oncology 107 (2013) 389–391
0.5 times or more than that was diagnosed) and not responding to steroid (symptom or sign showed no change or more serious; The patchy shadow or obscured-glass shadow on CT image showed no change or evolved) (Table 1 and Fig. 1).
391
A blood sample was collected from each patient in the case group at three time points: the onset of RP diagnosis, 1 month and 3 months after diagnosis, while blood from the control group was collected 3 months after radiotherapy. The serum was separated and then stored at 80 °C condition. The measurement was performed using a sandwich-type electrochemiluminescence immunoassay kit (Mouse CD36/ SR-B3 Affinity Purified Polyclonal Ab, Goat IgG; R&D systems, America). It was performed in duplicate.
increased obviously at the onset of RP than the control group. The serum CD36 levels at the onset of RP showed significant difference between different grades. After treatment with steroid, CD36 levels showed decrease in the steroid-effective group while were not seen in the non-effective group. Therefore, CD36 may become an important index for predicting the occurrence and development of radiation pneumonitis and assessing the radiation-induced lung injury extent and treatment effect by steroid. However, the current study had a limited number of patients in this research and reports the relationship between CD36 and radiation pneumonitis is rare and the change of human circulating cytokines may be affected by many factors. Whether CD36 could become an important factor for assessing the occurrence, development and treatment effect of radiation pneumonitis needs further investigation.
Statistical analysis
References
We used SPSS13.0 for statistical analysis. The data were shown by mean ± standard deviation. The differences among different groups were assessed by t-test, one way analysis of variance and Mann–Whitney U test. Statistical significance was defined as P < 0.05.
[1] Rodemann HP. Molecular radiation biology: perspectives for radiation oncology. Radiother Oncol 2009;92:293–8. [2] Stewart FA, Dorr W. Milestones in normal tissue radiation biology over the past 50 years: from clonogenic cell survival to cytokine networks and back to stem cell recovery. Int J Radiat Biol 2009;85:574–86. [3] Machtay M. Pulmonary complications of anticancer treatment. 3rd ed. Churchill Livingston; 2003. [4] Wang JY, Chen KY, Wang JT, et al. Outcome and prognostic factors for patients with non-small-cell lung cancer and severe radiation pneumonitis. Int J Radiat Oncol Biol Phys 2002;54:735–41. [5] Robnett TJ, Machtay M, Vines EF, et al. Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys 2000;48:89–94. [6] Hughes-Davies L, Tarbell NJ, Coleman CN, et al. Stage IA-IIB Hodgkin’s disease: management and outcome of extensive thoracic involvement. Int J Radiat Oncol Biol Phys 1997;39:361–9. [7] Marks LB, Fan M, Clough R, et al. Radiation-induced pulmonary injury: symptomatic versus subclinical endpoints. Int J Radiat Biol 2000;76:469–75. [8] Trott KR, Herrmann T, Kasper M. Target cells in radiation pneumopathy. Int J Radiat Oncol Biol Phys 2004;58:463–9. [9] Rube CE, Rodemann HP, Rube C. The relevance of cytokines in the radiationinduced lung reaction. Experimental basis and clinical significance. Strahlenther Onkol 2004;180:541–9. [10] Tsoutsou PG, Koukourakis MI. Radiation pneumonitis and fibrosis: mechanisms underlying its pathogenesis and implications for future research. Int J Radiat Oncol Biol Phys 2006;66:1281–93. [11] Azuma A, Li YJ, Abe S, et al. Interferon-b inhibits bleomycin-induced lung fibrosis by decreasing transforming growth factor-b 1 and thrombospondin. Am J Respir Cell Mol Biol 2005;32:93–8. [12] Brown JM, Swindle EJ, Kushnir-Sukhov NM, Holian A, Metcalfe DD. Silicadirected mast cell activation is enhanced by scavenger receptors. Am J Respir Cell Mol Biol 2007;36:43–52. [13] Yehualaeshet T, O’Connor R, Green-Johnson J, et al. Activation of rat alveolar macrophage-derived latent transforming growth factor-b1 by plasmin requires interaction with thrombospondin-1 and its cell surface receptor, CD36. Am J Pathol 1999;155:841–51. [14] Hara R, Itami J, Komiyama T, et al. Serum levels of KL-6 for predicting the occurrence of radiation pneumonitis after stereotactic radiotherapy for lung tumors. Chest 2004;125:340–4. [15] Iwata Hiromitsu, Shibamoto Yuta, Baba Fumiya, et al. Correlation between the serum KL-6 level and the grade of radiation pneumonitis after stereotactic body radiotherapy for stage I lung cancer or small lung metastasis. Radiother Oncol 2011;101:267–70. [16] Wang Xin, Chen Ying, Lv Lina, et al. Silencing CD36 gene expression results in the inhibition of latent-TGF-b activation and suppression of silica-induced lung fibrosis in the rat. Respir Res 2009;10:36. [17] Yehualaeshet T, O’Connor R, Begleiter A, et al. A CD36 synthetic peptide inhibits bleomycin-induced pulmonary inflammation and connective tissue synthesis in the rat. Am J Respir Cell Mol Biol 2000;23:204–12.
Serum CD36 assay
Results We got 23 cases with Grade 2 RP, 7 cases with PGrade 3 RP. Out of 30 RP patients, 2 cases died from respiratory failure and other 28 cases were followed up for 3 months. The serum CD36 levels increased significantly in RP group at onset of diagnosis when compared with the control group (Table 2). In RP group, CD36 levels showed significant improvement after steroid treatment (P < 0.05) totally. CD36 levels in 18 cases responding to steroid significantly decreased while 10 cases not responding to steroid did not show obvious change (Table 3). Furthermore, the CD36 mean levels at the onset of RP was 26.86 ± 1.75 pg/ml in Grade 2 RP patients and 31.91 ± 6.33 pg/ml in PGrade 3 RP patients (P < 0.05) which indicated that serum CD36 levels increased with the aggravation of RP. Discussion Our research examined the relationship of serum CD36 level with radiation-induced pneumonitis (RP). Our study first demonstrated that the serum CD36 level increased significantly at the onset of RP diagnosis and the level increased with pulmonary injury aggravated. The serum CD36 level significantly decreased when responded to steroid therapy in RP patients. Researches on the pathogenesis of radiation pneumonitis revealed a number of biological [14,15] factors could serve as a predictive marker of RP. Transforming growth factor-1 (TGF-1) is a strong profibrogenic factor that promotes the deposition of extracellular matrix and plays a critical role in the development of radiation pneumonitis. As a receptor for thrombospondin-1 (TSP-1), CD36 had been identified to be an important activator for TGF-1 [16,17] in its profibrogenic pathway in the process of lung fibrosis. In this study, the serum CD36 levels
Contents lists available at SciVerse ScienceDirect
Radiotherapy and Oncology journal homepage: www.thegreenjournal.com
Morbidity of lung cancer RT
The CD36 dynamic change after radiation therapy in lung cancer patients and its correlation with symptomatic radiation pneumonitis Lu Bai b, Junhua Zhao c, Hong Yu d, Na Zhao a, Dan Liu a, Wen Zhong a, Yuxia Zhao a,⇑ a
Department of Radiation Oncology, Fourth Affiliated Hospital of China Medical University; b Department of Radiation Oncology, First Affiliated Hospital of China Medical University; c Department of the Seven-year clinics of China Medical University; d Department of Radiation Oncology, Liaoning Cancer and Institute, People’s Republic of China
a r t i c l e
i n f o
Article history: Received 22 February 2012 Received in revised form 28 March 2013 Accepted 14 April 2013 Available online 14 May 2013
a b s t r a c t This study was carried out to investigate the relationship between serum CD36 levels and radiation pneumonitis in 30 patients irradiated for lung cancer. We found CD36 may become an important index for predicting the occurrence and development of radiation pneumonitis and evaluating the curative effect. Ó 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 107 (2013) 389–391
Keywords: Radiation-induced pneumonitis Lung cancer CD36 Radiotherapy
Radiation-induced inflammation plays a critical role in normal tissue response. Normal tissue injury involves complex interactions, including damage to parenchymal cells, vasculature, endothelial cells, stroma and interactions with and response of the tissue micro-environment, particularly the effects of inflammatory cytokines [1,2]. Thoracic radiotherapy is limited by the high radiosensitivity of the normal lung parenchyma [3,4]. It was reported that the clinically significant radiation lung injury occurred in up to 30% of patients irradiated for lung cancer [5] and about 10– 15% of other thoracic oncology patients [6]. Besides, a larger proportion of patients will have subclinical adverse effects of radiation on the lung, which can be identified by imaging and/or physiologic testing [7]. There are two types of radiation lung injury. Acute radiation pneumonopathy (pneumonitis) can occur several weeks to six months post-irradiation with cough, shortness of breath, fever and changes in pulmonary function. The second type of radiation – induced lung injury is referred to the ‘‘fibrotic’’ phase months to years after irradiation. Although the pathogenesis of RP remains unclear, several studies have reported that a variety of cytokines, chemokines, were involved in [8–10] the inflammatory process of RP. Transforming growth factorb-1 (TGFb-1) had been [11,12] identified playing a critical role in the occurrence and development of lung fibrosis. The activation of TGFb-1 needs the regulation by CD36. CD36 could regulate the production of collagen by the way ⇑ Corresponding author. Address: Department of radiation oncology, The fourth affiliated hospital of China Medical University, No. 4, Eastern Chongshan Road, Huanggu District, Shenyang 110032, People’s Republic of China. E-mail address: [email protected] (Y. Zhao). 0167-8140/$ - see front matter Ó 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.radonc.2013.04.014
of acting on the pro-fibrogenic pathway of TGF-b1. In the lung fibrosis module of bleomycin-induced rat, the activated TGF-b1 (released by alveolar macrophage) decreased when the rat was administered CD36 antibody and the synthesis of inflammation and connective tissue also decreased [13]. However, there is no report on the relationship between serum CD36 level and radiationinduced pneumonitis. Whether CD36 could become a reliable predictor for radiation-induced pneumonitis?
Material and methods Patients The case group included 30 RP patients with lung cancer after thoracic three dimensional conformal radiotherapy from December 2008 to May 2011. The control group was established from 30 patients with lung cancer without RP after radiation by case– control study with frequency matched principle. All participants were recruited at the first affiliated hospital of China Medical University and Liaoning Cancer Hospital and Institute. All patients presented with histologically or cytologically confirmed lung cancer, with no history of pulmonary radiotherapy, a Karnofsky performance status of >60, and an expected survival of >6 months. The exclusion criteria included pneumonectomy, severe cardiopulmonary disease and diabetes. This study was approved and supported by the institutional review board of the first affiliated hospital of China Medical University. Written, informed consent was obtained from each patient for the use of blood and clinical data. It was a retrospective study.
390
The CD36 dynamic change in patients with radiation pneumonitis
Table 1 Scoring criteria for evaluation after steroid treatment. Responding to steroid
Table 2 CD36 levels in RP group and control group (pg/ml). Not responding to steroid
Symptom
Improved
CT image
Contracted 0.5 times or more than that was diagnosed
RP group CD36 levels
No change or more serious No change or evolved
a b
28.07 ± 4.80
Control group a
17.09 ± 1.95
b
P value <0.05
Onset of RP diagnosis. 3 Months after radiotherapy.
Table 3 Change of serum CD36 levels during different time points (pg/ml).
Evaluation of RP Physical examination and computed tomography (CT) were performed at the onset of RP, 1 month and 3 months after diagnosis. Common Terminology Criteria for Adverse Events version 3.0 were used to grade RP, as follows: grade 0, no change; grade 1, asymptomatic radiographic findings only; grade 2, symptomatic, not interfering with activities of daily living; grade 3, symptomatic, interfering with activities of daily living, O2 therapy required; grade 4, life-threatening ventilatory support required; and grade 5, severe pneumonitis resulting in death. The evaluation was accomplished by two veteran radiologists together. Patients with RP P Grade 2 were selected for our research. Grade 1 RP was not included in our study.
Therapeutic strategy and evaluation after treatment The patients with radiation pneumonitis (RP) were diagnosed when they come to hospital with respiratory symptoms. ‘‘1 month and 3 month after diagnosis of RP’’ refers to the evaluation time points of treatment effect by methylprednisolone. All RP patients in the case group received methylprednisolone therapy after diag-
Onset of RP 1 Month after diagnosis 3 Months after diagnosis
Total group
Responding to steroid
Not responding to steroid
27.67 ± 3.40 23.99 ± 8.93*
27.35 ± 1.25 18.61 ± 1.58
28.49 ± 5.75 33.68 ± 8.49**
20.88 ± 8.58*
15.44 ± 1.42
30.66 ± 7.17**
*
P < 0.05, CD36 levels decreased significantly by steroid treatment after diagnosis. P < 0.05, CD36 levels decreased significantly in patients responding to steroid, while not shown in patients not responding to steroid.
**
nosis. The original dosage was 32 mg once a day, with 8 mg decreased weekly for 4 weeks. There were two time points for the effect evaluation by steroid treatment: 1 month and 3 months after diagnosis. The treatment effect was evaluated according to the improvement of clinical symptom, CT image and pulmonary function. The evaluation criteria were divided into responding to steroid (symptom improved with cough or dyspnea release, temperature decrease, the moist rale reduce or disappear; The patchy shadow or obscured-glass shadow on CT image contracted
(a) when diagnosis
(b) 1 month after diagnosis
Fig. 1. CT images of a RP patient during diagnosis (a) and 1 month after diagnosis (b).
L. Bai et al. / Radiotherapy and Oncology 107 (2013) 389–391
0.5 times or more than that was diagnosed) and not responding to steroid (symptom or sign showed no change or more serious; The patchy shadow or obscured-glass shadow on CT image showed no change or evolved) (Table 1 and Fig. 1).
391
A blood sample was collected from each patient in the case group at three time points: the onset of RP diagnosis, 1 month and 3 months after diagnosis, while blood from the control group was collected 3 months after radiotherapy. The serum was separated and then stored at 80 °C condition. The measurement was performed using a sandwich-type electrochemiluminescence immunoassay kit (Mouse CD36/ SR-B3 Affinity Purified Polyclonal Ab, Goat IgG; R&D systems, America). It was performed in duplicate.
increased obviously at the onset of RP than the control group. The serum CD36 levels at the onset of RP showed significant difference between different grades. After treatment with steroid, CD36 levels showed decrease in the steroid-effective group while were not seen in the non-effective group. Therefore, CD36 may become an important index for predicting the occurrence and development of radiation pneumonitis and assessing the radiation-induced lung injury extent and treatment effect by steroid. However, the current study had a limited number of patients in this research and reports the relationship between CD36 and radiation pneumonitis is rare and the change of human circulating cytokines may be affected by many factors. Whether CD36 could become an important factor for assessing the occurrence, development and treatment effect of radiation pneumonitis needs further investigation.
Statistical analysis
References
We used SPSS13.0 for statistical analysis. The data were shown by mean ± standard deviation. The differences among different groups were assessed by t-test, one way analysis of variance and Mann–Whitney U test. Statistical significance was defined as P < 0.05.
[1] Rodemann HP. Molecular radiation biology: perspectives for radiation oncology. Radiother Oncol 2009;92:293–8. [2] Stewart FA, Dorr W. Milestones in normal tissue radiation biology over the past 50 years: from clonogenic cell survival to cytokine networks and back to stem cell recovery. Int J Radiat Biol 2009;85:574–86. [3] Machtay M. Pulmonary complications of anticancer treatment. 3rd ed. Churchill Livingston; 2003. [4] Wang JY, Chen KY, Wang JT, et al. Outcome and prognostic factors for patients with non-small-cell lung cancer and severe radiation pneumonitis. Int J Radiat Oncol Biol Phys 2002;54:735–41. [5] Robnett TJ, Machtay M, Vines EF, et al. Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys 2000;48:89–94. [6] Hughes-Davies L, Tarbell NJ, Coleman CN, et al. Stage IA-IIB Hodgkin’s disease: management and outcome of extensive thoracic involvement. Int J Radiat Oncol Biol Phys 1997;39:361–9. [7] Marks LB, Fan M, Clough R, et al. Radiation-induced pulmonary injury: symptomatic versus subclinical endpoints. Int J Radiat Biol 2000;76:469–75. [8] Trott KR, Herrmann T, Kasper M. Target cells in radiation pneumopathy. Int J Radiat Oncol Biol Phys 2004;58:463–9. [9] Rube CE, Rodemann HP, Rube C. The relevance of cytokines in the radiationinduced lung reaction. Experimental basis and clinical significance. Strahlenther Onkol 2004;180:541–9. [10] Tsoutsou PG, Koukourakis MI. Radiation pneumonitis and fibrosis: mechanisms underlying its pathogenesis and implications for future research. Int J Radiat Oncol Biol Phys 2006;66:1281–93. [11] Azuma A, Li YJ, Abe S, et al. Interferon-b inhibits bleomycin-induced lung fibrosis by decreasing transforming growth factor-b 1 and thrombospondin. Am J Respir Cell Mol Biol 2005;32:93–8. [12] Brown JM, Swindle EJ, Kushnir-Sukhov NM, Holian A, Metcalfe DD. Silicadirected mast cell activation is enhanced by scavenger receptors. Am J Respir Cell Mol Biol 2007;36:43–52. [13] Yehualaeshet T, O’Connor R, Green-Johnson J, et al. Activation of rat alveolar macrophage-derived latent transforming growth factor-b1 by plasmin requires interaction with thrombospondin-1 and its cell surface receptor, CD36. Am J Pathol 1999;155:841–51. [14] Hara R, Itami J, Komiyama T, et al. Serum levels of KL-6 for predicting the occurrence of radiation pneumonitis after stereotactic radiotherapy for lung tumors. Chest 2004;125:340–4. [15] Iwata Hiromitsu, Shibamoto Yuta, Baba Fumiya, et al. Correlation between the serum KL-6 level and the grade of radiation pneumonitis after stereotactic body radiotherapy for stage I lung cancer or small lung metastasis. Radiother Oncol 2011;101:267–70. [16] Wang Xin, Chen Ying, Lv Lina, et al. Silencing CD36 gene expression results in the inhibition of latent-TGF-b activation and suppression of silica-induced lung fibrosis in the rat. Respir Res 2009;10:36. [17] Yehualaeshet T, O’Connor R, Begleiter A, et al. A CD36 synthetic peptide inhibits bleomycin-induced pulmonary inflammation and connective tissue synthesis in the rat. Am J Respir Cell Mol Biol 2000;23:204–12.
Serum CD36 assay
Results We got 23 cases with Grade 2 RP, 7 cases with PGrade 3 RP. Out of 30 RP patients, 2 cases died from respiratory failure and other 28 cases were followed up for 3 months. The serum CD36 levels increased significantly in RP group at onset of diagnosis when compared with the control group (Table 2). In RP group, CD36 levels showed significant improvement after steroid treatment (P < 0.05) totally. CD36 levels in 18 cases responding to steroid significantly decreased while 10 cases not responding to steroid did not show obvious change (Table 3). Furthermore, the CD36 mean levels at the onset of RP was 26.86 ± 1.75 pg/ml in Grade 2 RP patients and 31.91 ± 6.33 pg/ml in PGrade 3 RP patients (P < 0.05) which indicated that serum CD36 levels increased with the aggravation of RP. Discussion Our research examined the relationship of serum CD36 level with radiation-induced pneumonitis (RP). Our study first demonstrated that the serum CD36 level increased significantly at the onset of RP diagnosis and the level increased with pulmonary injury aggravated. The serum CD36 level significantly decreased when responded to steroid therapy in RP patients. Researches on the pathogenesis of radiation pneumonitis revealed a number of biological [14,15] factors could serve as a predictive marker of RP. Transforming growth factor-1 (TGF-1) is a strong profibrogenic factor that promotes the deposition of extracellular matrix and plays a critical role in the development of radiation pneumonitis. As a receptor for thrombospondin-1 (TSP-1), CD36 had been identified to be an important activator for TGF-1 [16,17] in its profibrogenic pathway in the process of lung fibrosis. In this study, the serum CD36 levels