Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.
Kim, Seung Joon;Lee, Jung Mi;Kim, Jin Sook;Kang, Ji Young;Lee, Sang Hak;Kim, Seok Chan;Lee, Sook Young;Kim, Chi Hong;Ahn, Joong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Song, Jeong Sup;Park, Sung Hak;Moon, Seok Hwan;Wang, Yeong Pil
Tuberculosis and Respiratory Diseases
/
v.64
no.3
/
pp.200-205
/
2008
Background: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. Methods: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. Results: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. Conclusion: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.
Kim, Ae-Kyoung;Jeong, Seong-Su;Shin, Kyoung-Sang;Park, Sang-Gee;Jo, Hai-Jeong;Lee, Jong-Jin;Seo, Jee-Won;Kim, Ju-Ock;Kim, Sun-Young
Tuberculosis and Respiratory Diseases
/
v.42
no.4
/
pp.502-512
/
1995
Background: One quarter to one third of patients with NSCLC present with primary tumors that although confined to the thorax are too extensive for surgical resection. Until resently standard treatment for these patients had been thoracic radiation, which produces tumor regression in most patients but few cures and dismal 5-year survival rate. The fact that death for most patients with stage III tumors is caused by distant metastases has promped a reevaluation of combined modality treatment approaches that include systemic chemotherapy. Therefore, we report the results observed in a study to evaluate the effect of multimodality treatment in locally advanced non-small cell lung cancer from 1/91 to 8/93 in CNUH. Method: We grouped the patients according to the treatment modalities and evaluated response rate, median survival and the effect of prognostic variables. Among 67 patients evaluated, twenty seven patients classified with group A, received cisplatin and etoposide containing combination chemotherapy alone, eighteen patients, classified with group B, received chemotherapy and radiotherapy, fifteen patients, group C, received neoadjuvant or adjuvant chemotherapy and surgery with/without radiation therapy, seven patients, group D, received only supportive care. Result: The major response rate for group A and B was 37% and 61% respectively. There was no statistically significant difference in response rate between A and B groups(p=0.97). The analysis of prognostic factors showed that differences of age, sex, pathology, blood type, smoking year, stage and ECOG performance did not related to improvement in survival. Median survival time was 8.6 months for group A, 13.4 months for group B, 19.2 months for group C, and 5.4 months for group D, respectively and there was statistically significant difference(p=0.003), suggesting that multimodality therapy was associated with signigicant improvement in survival. Subset survival analysis showed a significant therapeutic effect for earlier stage and good performance state(p=0.007, 0.009, respectively). A possible survival advantages were observed for major response groups. Conclusion: It was suggested that multimodality therapy for the management of patients who had stage III disease, has yielded good median survival and long survival for seleted patients. But, it is necessory to validate above result with further investigation in large scale and in prospective randomized trials.
Park, So-Yeon;Ahn, Jong-Ho;Suh, Jung-Min;Kim, Yung-Il;Kim, Jin-Man;Choi, Byung-Ki;Pyo, Hong-Ryul;Song, Ki-Won
The Journal of Korean Society for Radiation Therapy
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v.24
no.2
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pp.123-135
/
2012
Purpose: It is essential to minimize the movement of tumor due to respiratory movement at the time of respiration controlled radiotherapy of non-small cell lung cancer patient. Accordingly, this Study aims to evaluate the usefulness of restricted respiratory period by comparing and analyzing the treatment plans that apply free and restricted respiration period respectively. Materials and Methods: After having conducted training on 9 non-small cell lung cancer patients (tumor n=10) from April to December 2011 by using 'signal monitored-breathing (guided- breathing)' method for the 'free respiratory period' measured on the basis of the regular respiratory period of the patents and 'restricted respiratory period' that was intentionally reduced, total of 10 CT images for each of the respiration phases were acquired by carrying out 4D CT for treatment planning purpose by using RPM and 4-dimensional computed tomography simulator. Visual gross tumor volume (GTV) and internal target volume (ITV) that each of the observer 1 and observer 2 has set were measured and compared on the CT image of each respiratory interval. Moreover, the amplitude of movement of tumor was measured by measuring the center of mass (COM) at the phase of 0% which is the end-inspiration (EI) and at the phase of 50% which is the end-exhalation (EE). In addition, both observers established treatment plan that applied the 2 respiratory periods, and mean dose to normal lung (MDTNL) was compared and analyzed through dose-volume histogram (DVH). Moreover, normal tissue complication probability (NTCP) of the normal lung volume was compared by using dose-volume histogram analysis program (DVH analyzer v.1) and statistical analysis was performed in order to carry out quantitative evaluation of the measured data. Results: As the result of the analysis of the treatment plan that applied the 'restricted respiratory period' of the observer 1 and observer 2, there was reduction rate of 38.75% in the 3-dimensional direction movement of the tumor in comparison to the 'free respiratory period' in the case of the observer 1, while there reduction rate was 41.10% in the case of the observer 2. The results of measurement and comparison of the volumes, GTV and ITV, there was reduction rate of $14.96{\pm}9.44%$ for observer 1 and $19.86{\pm}10.62%$ for observer 2 in the case of GTV, while there was reduction rate of $8.91{\pm}5.91%$ for observer 1 and $15.52{\pm}9.01%$ for observer 2 in the case of ITV. The results of analysis and comparison of MDTNL and NTCP illustrated the reduction rate of MDTNL $3.98{\pm}5.62%$ for observer 1 and $7.62{\pm}10.29%$ for observer 2 in the case of MDTNL, while there was reduction rate of $21.70{\pm}28.27%$ for observer 1 and $37.83{\pm}49.93%$ for observer 2 in the case of NTCP. In addition, the results of analysis of correlation between the resultant values of the 2 observers, while there was significant difference between the observers for the 'free respiratory period', there was no significantly different reduction rates between the observers for 'restricted respiratory period. Conclusion: It was possible to verify the usefulness and appropriateness of 'restricted respiratory period' at the time of respiration controlled radiotherapy on non-small cell lung cancer patient as the treatment plan that applied 'restricted respiratory period' illustrated relative reduction in the evaluation factors in comparison to the 'free respiratory period.
The following conclusions were obtained after bibliographic investigation on the therapy of lung cancer by western, oriental, and integrated oriental and western medicine. 1. Lung cancer is classified into small cell lung cancer(SCLC) or non small cell lung cancer(NSCLC) in the treatment by western medicine, and applied with the means of surgery, radiotherapy and chemotherapy alone or combined, depending on the stage and the symptom. 2. Treatment by oriental medicine includes the means of strengthening body resistance to dispel pathogenic factors(扶正祛邪), combined approach of reinforcement and expulsion(攻補兼施), and reinforcing both qi and blood(氣血雙補), depending on the initial, middle, and terminal stage. And also treatment based on differentiation of symptom(辨證施治) is applied according to the type of symptom; deficiency of qi of both lung and spleen(肺脾氣虛), heat symptom of lung by deficiency of yin(肺熱陰虛), stagnation of damp-phlegm and blood(濕痰瘀阻), stagnation of qi and blood(氣血瘀滯), deficiency of both qi and yin(氣陰兩虛). Single or combined herb drug is used according to the symptom. 3. Treatment by integrated oriental and western medicine improved survival rate and quality of life. It promoted recovery and improved survival rate in the patients receiving surgery. Integrated radiotherapy and oriental medicine treatment reduced adverse effect by radiotherapy and improved therapeutic effect and survival rate. Integrated chemotherapy with oriental medicine treatment reduced side effect by chemotherapy and improved quality of life and survival rate. These results suggest that therapy of lung cancer should be applied with integrated oriental and western medicine from diagnosis to treatment for promoting therapeutic effect. And further study on this therapy should be ensued.
The application of a respiratory gated radiotherpy method to the lung radiation surgery was evaluated compared with the conventional method in which the whole tumor motion range is considered in the delineation of PTV (Planning target volume). The four dimensional CT simulation images were acquired for the five NSCLC (Non-small cell lung cancer) patients for radiation surgery. The respiratory gated plan was prepared with the 50% phase CT images and the conventional method was planned based on the ITV (Internal target volume) which include all the target volumes created in each phase CT images within a whole respiratory period. The DVH (Dose volume histogram) of OAR (Organ at risk) which calculated in each method was compared for the evaluation of the plan properness. The relative decrease of OARs' DVH were verified in the application of respiratory gated method. The average decrease rate were $16.88{\pm}9.97%$ in the bronchus, $34.13{\pm}19.15%$ in the spinal cord, $28.42{\pm}18.49%$ in the chest wall and $32.48{\pm}16.66%$ in the lung. Based on these results, we can verified the applicability and the effectiveness of the respiratory gated method in the lung radiation surgery.
The Journal of Korean Society for Radiation Therapy
/
v.26
no.1
/
pp.59-67
/
2014
Purpose : This study aims to evaluate 3D dosimetric impact for MIP image and each phase image in stereotactic body radiotherapy (SBRT) for lung cancer using volumetric modulated arc therapy (VMAT). Materials and Methods : For each of 5 patients with non-small-cell pulmonary tumors, a respiration-correlated four-dimensional computed tomography (4DCT) study was performed. We obtain ten 3D CT images corresponding to phases of a breathing cycle. Treatment plans were generated using MIP CT image and each phases 3D CT. We performed the dose verification of the TPS with use of the Ion chamber and COMPASS. The dose distribution that were 3D reconstructed using MIP CT image compared with dose distribution on the corresponding phase of the 4D CT data. Results : Gamma evaluation was performed to evaluate the accuracy of dose delivery for MIP CT data and 4D CT data of 5 patients. The average percentage of points passing the gamma criteria of 2 mm/2% about 99%. The average Homogeneity Index difference between MIP and each 3D data of patient dose was 0.03~0.04. The average difference between PTV maximum dose was 3.30 cGy, The average different Spinal Coad dose was 3.30 cGy, The average of difference with $V_{20}$, $V_{10}$, $V_5$ of Lung was -0.04%~2.32%. The average Homogeneity Index difference between MIP and each phase 3d data of all patient was -0.03~0.03. The average PTV maximum dose difference was minimum for 10% phase and maximum for 70% phase. The average Spain cord maximum dose difference was minimum for 0% phase and maximum for 50% phase. The average difference of $V_{20}$, $V_{10}$, $V_5$ of Lung show bo certain trend. Conclusion : There is no tendency of dose difference between MIP with 3D CT data of each phase. But there are appreciable difference for specific phase. It is need to study about patient group which has similar tumor location and breathing motion. Then we compare with dose distribution for each phase 3D image data or MIP image data. we will determine appropriate image data for treatment plan.
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