1.Expression of FLIP and its correlation with apoptosis in non-small cell lung cancer.
Yong CAO ; Qingquan LI ; Lihou ZHONG ; Ailing WANG
Chinese Journal of Lung Cancer 2003;6(1):51-54
BACKGROUNDTo investigate the relation between FLIP expression and apoptosis in non-small cell lung cancer (NSCLC).
METHODSFLIP expression was examined in forty-eight paraffin-embeded NSCLC samples and 16 benign pulmonary disease tissues by immunohistochemistry method. Apoptosis of NSCLC cells was detected by TUNEL technique.
RESULTSThe positive rate of FLIP expression in NSCLC was 83.33%(40/48), which was significantly higher than that in benign pulmonary disease tissues (P < 0.01). The expression level of FLIP was closely related to TNM stages and lymph node involvement, but not to histological classification and cell differentiation. No correlation was observed between the expression of FLIP and apoptosis index of tumor cells (r=-0.211,P > 0.05 ).
CONCLUSIONSOverexpression of FLIP may be involved in the progression of NSCLC, but its expression may not be related to cell apoptosis in NSCLC.
2.Expressions of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 and their correlation with metastasis and prognosis in lung cancer.
Jun LIANG ; Mingqiu LIN ; Mei XIE ; Xuan LIU
Chinese Journal of Lung Cancer 2003;6(1):46-50
BACKGROUNDTo investigate the expressions of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) and their correlation with metastasis and prognosis in human lung cancer.
METHODSImmunohistochemical S-P method was used to detect the expression of MMP-9 and TIMP-1 in 65 lung cancer tissues, 35 hyperplastic and dysplastic epithelium from patients with non-cancerous pulmonary diseases, and 30 normal epithelial tissues of the lung.
RESULTSThe positive expression rates of MMP-9 in normal tissue, hyperplastic or dysplastic epithelium, and lung cancer tissue were 16.7%(5/30), 42.9%(15/35) and 72.3%(47/65) respectively, whereas the positive rates of TIMP-1 expression in normal tissue, hyperplastic or dysplastic epithelium, and lung cancer tissue were 6.7%(2/30), 28.6%(10/35) and 50.8%(33/65) respectively. Significant differences of the expression rates of MMP-9 and TIMP-1 were found between lung cancer and normal groups, between lung cancer and hyperplasia groups, and between hyperplasia and normal groups (P < 0.05). Small cell carcinoma and adenocarcinoma had higher MMP-9 expression than squamous cell carcinoma (P < 0.025). Expression rate of MMP-9 had negative relation with cell differentiation of lung cancer (P < 0.05), and positive relation with TNM stage (P < 0.025). Between the survival time < 2 years group and ≥2 years groups, both the expressions of MMP-9 and TIMP-1 had significant difference (P < 0.05 ). The expression of MMP-9 was closely related to metastasis of lung cancer (P < 0.005), but the expression of TIMP-1 was not related to metastasis.
CONCLUSIONSOverexpression of MMP-9 may appear in precancerous lesion and at the early stage of lung cancer. Activation of MMP-9 gene may be an important factor for oncogenesis of the lung. MMP-9 and TIMP-1 may play important roles in lung cancer invasion and metastasis, their overexpression could act as a reference to evaluate metastasis and unfavourable prognosis of lung cancer.
3.A multicenter randomized phase II trial of domestic product of nrhTNF in the treatment of non-small cell lung cancer.
Qinghua ZHOU ; Mei HOU ; Lu LI ; Li REN ; Meng QIU ; Yuqiong YANG ; Wenxia HUANG ; Zhen CHEN ; Zhiqiang MENG ; Mingzhi SONG ; Mingzhong LI ; Enxiao LI ; Yi LI ; Yu YAO ; Zhiwen ZHENG ; Xing LIU ; Xiangfu ZHANG ; Huishan LU ; Maohong ZHANG ; Xiuwen WANG ; Xuejun YU
Chinese Journal of Lung Cancer 2003;6(1):42-45
BACKGROUNDTo evaluate and compare the effects and toxicity of the domestic product of nrhTNF combined with chemotherapy in the trial group and chemotherapy alone in the control group in the treatment of patients with non-small cell lung cancer (NSCLC).
METHODSNinety patients with NSCLC in multicenter were randomly devided into trial group and control group. Each group had 45 patients. Chemotherapy with CAP regimen was given for the patients in the trial group. Meanwhile, nrhTNF injection of 4×10⁶U/m ² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy course. Twenty-one days were as a cycle, 2 cycles were given each patients. Chemotherapy alone with CAP regimen was given in the control group. The chemothepeutic effects and toxicity were observed and compared between the two groups after the therapy.
RESULTSOf the 90 patients, 3 cases in each group were out of the trial because of economy. The other 84 cases (each group had 42 patients) could be used to analyze and evaluate the clinical effects and toxicity. The response rate of chemotherapy was 47.62% (20/42) in the trial group and 19.05% (8/42) in the control group (P=0.002) respectively. The KPS was 85.02±10.74 in the trial group, and 81.35±9.63 in the control group (P=0.038). No significant difference of degree III+IV toxicity was observed between the trial group and control group (P > 0.05). The side effects related to nrhTNF included slight fever, cold like symptoms, pain, and red and swelling in injection site. All of them were mild and didn't need any treatment and disappeared after the therapy.
CONCLUSIONSThe results demonstrate that the effects of domestic nrhTNF combined with chemotherapy can remarkably higher than that of chemotherapy alone in the treatment of NSCLC. It is able to increase the sensitivity to chemotherapy and improve the quality of life of the patients. The toxicity is also slight and is worth to expand clinical use, so as to further evaluate its effect and toxicity.
4.The staging of pulmonary angiography with the multi-slice spiral CT: to evaluate its significance in cancerous invasion of central pulmonary artery in lung cancer.
Xiaohua ZHU ; Jiaan DING ; Guozhen ZHANG ; Jingyun SHI ; Jiang SHAO ; Zhengqian YOU
Chinese Journal of Lung Cancer 2003;6(1):38-41
BACKGROUNDTo explore the possibility of the staging of pulmonary angiography with multi slice spiral CT (MSCT) and to evaluate its value in making surgical plan for patients with lung cancer.
METHODSMSCT with two-segment injection and three-protocol scan was performed in 73 patients with central type lung cancer. According to the site and degree, the involvement of pulmonary artery was divided into three grades and blindly compared with the surgery and pathology.
RESULTSMSCT in 68 cases (93.15%, 68/73) was successfully performed. The involvement of central pulmonary artery was grade I in 4 cases (5.88%, 4/68), grade II in 9 (13.23%, 9/68), and grade III in 55 (80.88%, 55/68). All patients with grade I underwent lobectomy. There was remarkable difference of lobectomy ratio between grade II and III (Chi-square=64.03, P < 0.005) and also between IIIa and IIIb (Chi-square=68.69, P < 0.005). All patients with grade IIIc were ruled out from surgery.
CONCLUSIONSThe staging of pulmonary angiography by MSCT is useful to demonstrate the site and degree of involvement of central pulmonary artery and provides more precise evidence of images for making surgical plan.
5.A study on the pericancerous tissue and vascular changes in non-small cell lung cancer with high-resolution CT.
Zhongxi NIU ; Qinghua ZHOU ; Xiao LI ; Gang ZHANG
Chinese Journal of Lung Cancer 2003;6(1):35-37
BACKGROUNDTo investigate the CT changes of pericancerous tissues with high-resolution CT (HRCT) and to explore the specific signs of CT in non-small cell lung cancer.
METHODSThirty-one patients with non-small cell lung cancer and 12 patients with benign pulmonary nodules were analysed. An attention was paid on bronchovascular bundles, vessels and interlobular septa. HRCT films were read independently by two radiologists and results were statistically Chi-square tested.
RESULTSIn the cancer group, 20 cases (64.5%) had thickening of bronchovascular bundles, 15 cases (48.4%) angiectasis of superior lobular arteries, 13 cases (41.9%) angiectasis of superior lobular veins, 16 cases (51.6%) thickening of interlobular septa, and 5 cases (16.1%) ground-glass opacity. In benign pulmonary lesion group, the values were 2 (16.7%) , 1 (8.3%), 2 (16.7%), 6 (50.0%) and 5 (41.7%) cases respectively. Significant differences were found between the two groups in the thickening of bronchovascular bundles and the angiectasis of superior lobular arteries.
CONCLUSIONSThickening of bronchovascular bundles and angiectasis of superior lobular arteries are the specific signs of non-small cell lung cancer.
6.The relationship among CT appearances and dynamic enhancement and microvessel density of peripheral lung cancer.
Jianlin WU ; Wei LI ; Keli WANG ; Qingwei TAN ; Miaomiao WANG ; Huicong SHEN
Chinese Journal of Lung Cancer 2003;6(1):30-34
BACKGROUNDTo investigate the relationship among the CT appearances, the dynamic CT enhancement and the microvessel density (MVD) of peripheral lung cancer.
METHODSThirty-three patients with peripheral lung cancer proved by surgery and pathology underwent enhancement dynamic CT scan before operation, including 14 squamous cell carcinoma and 19 adenocarcinoma. The MVD was measured in resected tumor specimens with immunohistochemical method of LSAB.
RESULTSThe MVD value of adenocarcinoma was significantly higher than that of squamous cell carcinoma (63.4±11.9 versus 50.2±16.3, P < 0.05). The MVD values were higher in junction zone and interstitial areas than those in parenchymal areas, necrotic zones and scar areas of tumors. There were significant relationships among the MVD value and diameter of tumor, lobulation sign, vessel convergence sign, pleural retraction sign and lymph node metastasis (P < 0.05 ). The mean enhanced CT values was (43.4±11.8) HU in adenocarcinomas, and (34.6±10.7) HU in squamous cell carcinomas (P < 0.05). The CT values of both adenocarcinoma and squamous cell carcinoma had positive correlations to their corresponding MVD values (r=0.719, P < 0.01;r=0.819, P < 0.01).
CONCLUSIONSThe CT appearances and the enhanced CT values of peripheral lung carcinomas are closely related to their MVD values, which might be an indicator to identify the histological classification and to predict the malignant degree of tumor.
7.CT features and anatomic distribution of pleural dissemination in lung cancer.
Peiju ZHU ; Hongli BAI ; Fengqiong YI ; Jingtao MIAO ; Jianqun YU ; Zhigang YANG
Chinese Journal of Lung Cancer 2003;6(1):26-29
BACKGROUNDTo study the CT appearance of lung cancer combined with pleural dissemination and its anatomic characteristics.
METHODSCT findings of 32 cases of lung cancer with pleural dissemination proved by surgery and pathology were analyzed.
RESULTSThe main CT manifestations were pleural effusion (24 cases), visceral pleural dissemination with nodules (10 cases), parietal pleural dissemination with nodules (16 cases), and pleural thickening (31 cases). Out of the cases with visceral pleural disseminations, nodules distributed on the lung surface in 9 sites, while on the interlobular pleura in 10 sites. Parietal pleural dissemination with nodules were found in 45 sites which located on the diaphragmatic pleura, the costal pleura, the mediastinal pleura, and the pulmonary ligament. The diameters of the small nodules ranged from 2 to 5 mm, and the large nodules from 5 to 10 mm. There were direct invasion with tumor induced pleural thickening in 10 cases, while indirect invasion in 21 cases. In the later cases, 9 cases had parietal pleural thickening less than 10 mm, 4 circumferential pleural thickening, 5 mediastinal pleural involvement thickening, and 3 pulmonary ligament thickening.
CONCLUSIONSPleural effusion is the main manifestation of lung cancer combined with pleural dissemination. The CT features of lung cancer with pleural dissemination are the parietal and visceral pleural nodules, as well as the pleural thickening. The nodules are likely to distribute on parietal pleura of the diaphragmatic and the costal pleura, and they may transfer to the pulmonary ligament.The early small disseminating nodules are miliary in size, and only can be detected on the pulmonary window of chest CT scan.
8.A preliminary application of MR dynamic time-resolved subtracted perfusion imaging to qualitative and partial quantitative evaluation of the blood supply by pulmonary artery in peripheral type lung cancer.
Zhengyu LI ; Jingtao MIAO ; Ying WANG ; Yunsheng HU
Chinese Journal of Lung Cancer 2003;6(1):22-25
BACKGROUNDTo explore the application of MR time-resolved subtracted perfusion imaging to qualitatively and partially quantitatively evaluate blood supply by pulmonary artery in patients with peripheral type lung cancer.
METHODSTwenty-three patients with peripheral type lung cancer proved cytologically or/and histologically underwent MR perfusion study. The time-resolved subtracted imaging which provided the perfusion images in different phases were performed. First-pass time-signal intensity curves of pulmonary artery, descending aorta, lung mass were obtained respectively, and start-time and peak-time of them were compared. The signal enhanced ratio of the masses in pulmonary artery and aorta perfusion phases were calculated respectively.
RESULTSFourteen masses began to enhance during pulmonary circulation phase and reached peak value during systematic-circulation phase, and the average signal change ratio during pulmonary circulation phase was much smaller than that during systematic-circulation phase, indicating their blood supply came both from pulmonary and systematic blood circulation, but mainly from the latter. Seven masses began to enhance and reached peak value during systematic-circulation phase, indicating their blood supply came mainly from systematic blood circulation. Two masses began to enhance and reached peak value during pulmonary-circulation phase, indicating their blood supply came mainly from pulmonary blood circulation.
CONCLUSIONSMR dynamic time-resolved subtracted perfusion imaging is feasible to qualitatively and relatively quantitatively evaluate blood supply of pulmonary artery for peripheral type lung cancer.
9.Preliminary study on the dynamic enhanced multi-slice spiral CT in the evaluation of blood flow patterns of malignant solitary pulmonary nodules.
Shenjiang LI ; Xiangsheng XIAO ; Shiyuan LIU ; Huimin LI ; Chengzhou LI ; Chenshi ZHANG ; Zhiwei TAO
Chinese Journal of Lung Cancer 2003;6(1):18-21
BACKGROUNDTo investigate the methods of dynamic enhanced multi-slice spiral CT in the evaluation of blood flow patterns of malignant solitary pulmonary nodules (SPNs).
METHODSFifty-seven patients with malignant SPNs (≤4 cm) underwent dynamic multi-slice spiral CT (Marconi Mx8000) scan before and after contrast enhancement by injecting 90 ml contrast material with a rate of 4 ml/s. Twenty-nine patients in protocol one were scanned every 2 seconds during 15-45 seconds and 75-105 seconds after injection, while 28 patients in protocol two were scanned every 2 seconds during 11-41 seconds and 71-101 seconds. All patients were then scanned every 30 seconds during 2-9 minutes. The collimation was 2.5 mm for lesions of ≤3 cm and 5 mm for lesions of 3-4 cm. Standard algorithm was used in the image reconstruction. The perfusion, peak height, ratio of peak height of the SPN to that of the aorta and mean transit time were calculated.
RESULTSThe enhancement value, perfusion, ratio of peak height of the SPN to that of the aorta and mean transit time were (34.61±11.37) HU, (31.17±11.18) ml/(min*100 g), 13.90%±4.15%, (13.96±5.86) s separately in protocol one, and (36.54±10.89) HU, (29.80±8.80) ml/(min*100 g), 15.01%±4.83%, (13.34±5.12) s respectively in protocol two. No statistically significant difference was found between the two groups. In addition, mean transit time from all 28 patients in protocol two were obtained, but only part of them were measured in protocol one (22/29).
CONCLUSIONSDynamic enhanced multi-slice spiral CT is a kind of non-invasive method for quantitative evaluation of blood flow patterns of malignant solitary pulmonary nodules. It might have potential significance in angiogenesis research for lung cancer.
10.The value of MR dynamic time-resolved subtracted imaging in evaluating the blood supply by systemic artery in patients with lung cancer.
Jingtao MIAO ; Ying WANG ; Zhengyu LI ; Yunsheng HU
Chinese Journal of Lung Cancer 2003;6(1):13-17
BACKGROUNDTo explore the application value of MR dynamic time-resolved subtracted imaging in qualitative and quantitative assessment of blood supply by systemic artery in patients with lung cancer.
METHODSA prospective study using MR FSPGR pulse sequence dynamic scan after contrast enhancement was undertaken in fifty-one patients with lung cancer which were proved by cytology or/and histology. The time-resolved subtracted imaging were acquired using the pre- and post-enhanced images in different phases of pulmonary circulation during the first-pass period (FPP) of contrast agent. The time-signal curves of FPP at four ROI placed on pulmonary artery (PA), descending aorta (DA), mass (M) and contralateral pulmonary parenchyma (PP), and the ST (start-time) and PT (peak-time) of those four ROI were measured. The enhancement ratio of the signals of M/PP at PA/DA peak time (E MP , E MA , E PP , E PA ) were calculated.
RESULTSAccording to the time-resolved subtracted imaging during PA phase, intensity of the signal was low in 7 cases, medium in 2, but not enhanced in other 42 cases. All the 51 cancer masses were remarkably enhanced during DA phase. During FPP, the ST [(5.90±0.51)s] and PT [(12.75±0.67)s] of PP were slightly later than the ST [(4.19±0.43)s] and PT [(10.59±0.66)s] of PA, while the ST [(11.03±0.80)s] and PT [(33.62±3.06)s] of cancer masses were later than ST [(9.43±0.59)s] and PT [(19.81±4.14)s] of DA. E MA was significantly higher than E MP (91.47%±18.83% vs 15.38%±11.03%, P < 0.001), while E PP were remarkably higher than E PA (273.83%±48.60% vs 140.65%±24.40%, P < 0.001).
CONCLUSIONSMR dynamic time-resolved subtracted imaging is feasible to be a non-invasive technique in qualitative and relatively quantitative assessment of blood supply by systemic artery in patients with lung cancer.