Cell-free DNA levels in plasma of patients with non-small-cell lung cancer and inflammatory lung disease.

BACKGROUND: The analysis of plasma cell-free DNA (cfDNA) is expected to provide useful biomarkers for early diagnosis of non-small-cell lung cancer (NSCLC). However, it remains unclear whether the intense release of cfDNA into the bloodstream of NSCLC patients results from malignancy or chronic inflammatory response. Consequently, the current diagnostic utility of plasma cfDNA quantification has not been thoroughly validated in subjects with chronic respiratory inflammation. Here we assess the effect of chronic respiratory inflammation on plasma cfDNA levels and evaluate the potential clinical value of this phenomenon as an early lung cancer diagnostic tool. METHODS: We measured plasma cfDNA concentrations in 50 resectable NSCLC patients, 101 patients with chronic respiratory inflammation (chronic obstructive pulmonary disease, sarcoidosis, or asthma) and 40 healthy volunteers using real-time PCR. RESULTS: We found significantly higher plasma cfDNA levels in NSCLC patients than in subjects with chronic respiratory inflammation and healthy individuals (P<0.0001). There were no significant differences in plasma cfDNA levels between patients with chronic respiratory inflammation and healthy volunteers. The cutoff point of >2.8 ng ml(-1) provided 90% sensitivity and 80.5% specificity in discriminating NSCLC from healthy individuals (area under the curve (AUC)=0.90). The receiver-operating characteristics curve distinguishing NSCLC patients from subjects with chronic respiratory inflammation indicated 56% sensitivity and 91% specificity at the >5.25-ng ml(-1) cutoff (AUC=0.76). CONCLUSIONS: We demonstrated that elevated plasma cfDNA levels in NSCLC resulted primarily from tumour development rather than inflammatory response, raising the potential clinical implications for lung cancer screening and early diagnosis. Further research is necessary to better characterise and identify factors and processes regulating cfDNA levels in the blood under normal and pathological conditions.

Vasodilatory effect and endothelial integrity in papaverine- and milrinone-treated human radial arteries.

Prevention of the vasospasm is an important aspect of coronary artery bypass grafting (CABG) with the use of radial artery (RA) as the conduit. We compared the effect of two phosphodiesterase inhibitors papaverine and milrinone on vasodilation and endothelial integrity of human RA segments harvested from 20 CABG patients. Vasodilatory effect of the drugs were assessed by organ bath technique in RA rings precontracted with KCl and phenylephrine. Endothelial integrity was evaluated by CD34 immunofluorescence in frozen sections. Vasorelaxation induced by papaverine was significantly greater as compared to that induced by milrinone (90.47% ± 10.16% vs. 78.98% ± 19.56%, p<0.05). Similarly, pretreament with papaverine more strongly inhibited the contractile response of RA rings to KCl (6.0 ± 8.0 mN vs. 26.7 ± 21.5 mN, p<0.001). Papaverine was also superior to milrinone in the preservation of endothelial integrity (75.3% ± 12.9% vs. 51.8% ± 18.0%, p<0.02). In conclusion, papaverine seems to be more suitable than milrinone for prevention of vasospasm in radial artery conduits used for CABG.

Neoadjuvant therapy affects tumor growth markers in early stage non-small-cell lung cancer.

INTRODUCTION: While adjuvant therapy of early-stage non-small-cell lung cancer (NSCLC) is widely accepted, literature data concerning neoadjuvant treatment provide contradictory results with both improved and unaffected survival rates. Also, data concerning potential effects of neo-adjuvant therapy on cellular level are scarce. OBJECTIVE: The aim of present study was to analyze the effect of chemotherapy followed by surgical resection on several key biological markers of tumor growth (TGF-beta, VEGF), apoptosis (sAPO-1/Fas/CD95) and invasiveness (TIMP-1) assessed in the sera of NSCLC early-stage patients (IB-IIIA). - MATERIAL AND METHODS: Measurements were performed by ELISA method in blood serum from 24 NSCLC patients (I-IIIA) collected prior therapy, one day before surgery and 3 days after. RESULTS: TGF-beta serum concentrations were significantly lower after both chemotherapy (P<0.05) and surgery (P<0.01) in comparison to the baseline. VEGF levels decreased following NEO therapy with subsequent significant up-regulation after surgery (P<0.001). Interestingly, post-surgery serum VEGF strongly correlated with TGF-beta concentration (r = 0.52, P = 0.014). No significant differences were observed for serum sAPO-1/CD95/FAS as well as TIMP-1 concentrations at any of three evaluated time-points. CONCLUSION: Neoadjuvant treatment of early-stage NSCLC affects mostly mechanisms responsible for tumor growth and vascularization. Its effect on cancer cells apoptotic activity needs further evaluation.

Superoxide dismutase activity and expression in human venous and arterial bypass graft vessels.

UNLABELLED: Venous bypass grafts are more prone to accelerated atherosclerosis than arterial grafts, which is partly related to increased oxidative stress and diminished nitric oxide bioavailability. In veins superoxide production is dependent primarily on nox2 NAD(P)H oxidase expression, while in arteries nox4 appears to play an important role. This may in part explain differences in susceptibility to graft failure. Net levels of oxidative stress are however determined in parallel by the production as well as by degradation of free radicals (eg. by superoxide dismutases, catalases, thioredoxins etc). The differences in superoxide dismutase (SOD) expression and activity in human bypass conduit vessels remain unclear. Accordingly, we aimed to compare SOD activity and protein levels as well as its functional effects on superoxide production in segments of human internal mammary arteries (IMA) and saphenous veins (HSV) from patients undergoing bypass graft surgery (n=24). SOD activity was assessed by inhibition of pyrogallol autoxidation, Cu-Zn SOD and Mn SOD protein levels were studied by immunoblotting. Basal superoxide release was detected by lucigenin (5 microM) enhanced chemiluminescence. Total SOD activity did not differ significantly between HSV and IMA. Similarly, no difference was observed in SOD activity in the presence of KCN (Mn-SOD). Human bypass conduit vessels show amounts of Cu-Zn SOD or Mn-SOD protein levels. In both HSV and IMA segments superoxide production was more than doubled in the presence of SOD inhibitor-DETC. CONCLUSIONS: These studies suggest that the differences in oxidative stress between human arteries and veins are unlikely to be caused by SOD activity. However SOD plays and important role in amelioration of oxidative stress in both types of vessels.

The conversion of thyroxine to triiodothyronine in the lung: comparison of activity of type I iodothyronine 5' deiodinase in lung cancer with peripheral lung tissues.

UNLABELLED: Triiodothyronine (T3) is the main active hormone, which is derived 20% from the thyroid gland and 80% from peripheral tissues. Thyroxin--5' deiodinases play a leading role in maintaining appropriate T3 concentrations in the different cells and organs: including the lung. The deiodinases present in pneumocytes were found to be localised in endoplasmatic reticulum. Aims of this study were: 1. To estimate activities of Type I and Type II iodothyronine 5' deiodinases (DI, DII) in two histological types of lung cancer. 2. To investigate possible differences in DI and DII activities between tumour tissue and peripheral lung tissue. 3. To study whether DI and DII activities are related to the extent of the disease process and grade of differentiation of lung cancer. MATERIAL: We studied 44 patients undergoing thoracotomy due to lung cancer. Histologically: 23 pts--squamous cell cancer, 21 pts adenocarcinoma. In all patients both tumour and peripheral lung tissue were studied. DI activity was measured in pmol 1251- released from 125 IrT3/min/mg of proteins, DII activity--in fmol 125I- released from 125IT4/hour/mg of protein. RESULTS: In most specimens DI and DII activities were observed. DI activity in specimens from lung peripheral tissue was: 3.3-58.3 pmol/min/mg of protein (mean 22.20) and in lung cancer tissue was: 2.0-44.7 pmol/min/mg of proteins (mean 13.3). DII activity in lung peripheral tissue ranged from 19 to 242 fmol/h/mg protein (mean 94.4) and in lung cancer ranged from 21 to 253 fmol/h/mg protein (mean 107.9). CONCLUSIONS: 1. Conversion of T4 to T3 occurs also in the lung. 2. The activity of DI is statistically significantly lower, in lung cancer than in peripheral lung tissue (13.3 +/- 9.5 vs 22.20 +/- 13.4 pmol/min/mg protein) respectively, p < 0.001. 3. DII activity in lung is present and similar in peripheral lung and lung cancer tissue. 4. There is a non-significant trend for correlation of DI activity and grade of differentiation (G1-G3) of tumour tissue and stage of lung cancer. Abbreviations' list: T3--triiodothyronine, T4--thyroxine, FT4--free thyroxine, rT3--revers triiodothyronine TSII--Thyroid Stimulating Hormone Type I lodothyronine 5'deiodinase = type I 5'deiodinase = 5'DI = DI Type II Iodothyronine 5'deiodinase = typeII 5'deiodinase = 5'DII = DII E.S.S.--Euthyroid Sick Syndrome, hDII = human type II iodothyronine deiodinase HDII-b, hDII-c = two novel splice variants SCC--Squamous Cell Cancer, A--adenocarcinoma, BMI--Body Mass Index BSA--Bovine Standard Albumin, DTT-1,4 Dithio-L-treitol, PTU--Propylothiouracil TCA--Tricholoroacetic Acid, TNM--Tumour Nodule Metastases (class.) G1-G3-grade of differentiation, COPD--Chronic Obstructive Pulmonary Disease.

[Primary lung hemangiopericytoma--a rare neoplasm with a long course of recurrence over many years]. / Pierwotny hemangiopericytoma pluca--rzadki nowotwór o nawracajacym, wieloletnim przebiegu.

Hemangiopericytoma (HPC) is a rare neoplasm arising from pericytes that occur mostly around smaller vessels. Up to now only about 100 cases have been reported to arise primarily in the lung. The behavior of pulmonary hemangiopericytomas is difficult to predict and all tumors should be considered potentially malignant, even though the criteria for malignancy are not well developed. The diagnosis of HPC is known to confound even experienced pathologist. Pericytes lack readily identifiable morphologic features, therefore hemangiopericytomas are often confused with other soft tissue tumors that may have hemangiopericytoma--like pattern. We report a rare case of primary HPC of the lung with an asymptomatic, long course of the disease. The diagnosis of hamartoma was established after the first operation. Subsequently, seven years later, a chest radiograph revealed new lesions. Histological examination, including immunohistochemistry lead to the final diagnosis of hemangiopericytoma. The small number of cases of primary pulmonary hemangiopericytoma makes it difficult to define the correct histopathological diagnosis especially without modern methods.

[Risk of hypertension after heart transplantation in the follow-up period]. / Ryzyko nadcisnienia tetniczego po przeszczepieniu serca w obserwacji odleglej.

From October 1988 to March 2000, 58 patients underwent orthotopic heart transplantation (HTX). Data of 220 heart recipients with the follow up > or = 3 months after HTX were analyzed using the average values of blood pressure measured with the sphigmo-manometer. 65% of patients were diagnosed with the hypertension (HA). 39.9% of those patients (NTA group) had the systolic blood pressure < or = 140 mmHg and diastolic blood pressure < or = 90 mmHg during pharmacotherapy. 60.1% of hypertensive patients (NTB group) had the systolic pressure > 140 mmHg and/or diastolic pressure > 90 mmHg despite pharmacotherapy. 35% of all patients had normal blood pressure after HTX (HNA group). Patients with hypertension were older and the end stage ischemic cardiomyopathy was more frequently indication for HTX. Significantly more females were in NTA group. We observed no influence of the daily dose of cyclosporine or other immunosuppressive drugs on HA. The average blood concentration of cyclosporine A and mycophenolate mofetil was similar in all groups. The calcium channel blockers and inhibitors of angiotensin converting enzyme were main tool of pharmacotherapy used. In NTA group calcium channels blockers were used more frequently. In NTB group there was a statistically significant higher blood level of creatinine. After HTX there is a high risk of HA, which: increases with age, with the ischemic cardiomyopathy as indication to HTX, is significantly higher in males, there is no correlation between HA and the dosage and blood level of cyclosporine, increases with kidney insufficiency. In monotherapy calcium channel blockers seem to be especially effective.

Changes in myocardial perfusion after transmyocardial laser revascularization in patients with end-stage angina pectoris.

The purpose of the present study was to analyze the effects of transmyocardial laser revascularization (TMLR) on myocardial perfusion. The value of (99m)Tc-MIBI scintigraphy in the detection of changes in perfusion of the lased and nonlased segments was assessed as well. In 15 patients before TMLR and then 3 and 6 months afterwards, MIBI scintigraphy and a stress test were carried out. At the beginning of the study, all patients were classified as having angina pectoris class III or IV (according to the criteria of the Canadian Cardiac Society); their ejection fraction was >30%. The parameters of the stress test increased significantly in 70% of the patients. Cardiac scintigraphy revealed improved perfusion of 33.7% of the transient defects within 3 months after TMLR which persisted at 6 months with a clear trend towards further improvement in the lased segments. TMLR has been found to be particularly beneficial in patients in whom other invasive methods of treatment cannot be applied.

Lung carcinoids. Tumor angiogenesis in relation to clinicopathologic characteristics.

OBJECTIVE: To evaluate the prognostic value of carcinoid angiogenesis for the presence of lymph node metastases, histologic subtype and tumor size. STUDY DESIGN: The study group consisted of 72 resected primary lung carcinoids, 57 typical and 15 atypical. TNM staging was performed. The histologic criteria for carcinoids was based on the Flieder classification. Angiogenesis, expressed as tumor microvessel density, was estimated in sections stained with CD34 antibody, according to Weidner's method. RESULTS: The size of carcinoids was related to the histologic type: the average tumor diameter of typical carcinoids was significantly smaller than the average diameter of atypical carcinoids (P = .003, U = 207, Z = -3.023). Atypical carcinoids represented a more aggressive form of tumors than typical carcinoids; patients with typical carcinoids developed lymph node metastases less frequently (10% vs. 33%) as compared to patients with atypical carcinoids; the difference was statistically significant (P = .032). Tumor angiogenesis failed to distinguish the histologic type of carcinoids and did not indicate the presence or absence of regional lymph node metastases; neither did pTN stage or tumor size. CONCLUSION: Angiogenesis is not a determining factor of the metastatic potential of pulmonary carcinoids.

Frequency and clinical significance of beta-subunit human chorionic gonadotropin expression in non-small cell lung cancer patients.

Human chorionic gonadotropin (HCG), a classic trophoblastic marker, has been found recently in many nontrophoblastic tumors. Previously we have found elevated serum betaHCG levels in 14% of small cell lung cancer patients. The aim of the present study was to assess the frequency and clinical significance of betaHCG expression in non-small cell lung tumors and in the sera of patients. 153 non-small cell lung cancer patients entered into this study. The control group consisted of 85 patients with benign lung diseases. Serum betaHCG elevation exceeding 5 mIU/ml was found in 3.5% of patients with benign lung diseases and in 12% of lung cancer patients (p = 0.03). Tumor analysis revealed the presence of betaHCG positivity in 28% of resected lung specimens. betaHCG positivity was found more often in adenocarcinoma than in squamous cell lung carcinoma both in tissue and in serum, the differences being not significant. Elevated serum betaHCG values were found more frequently in stage IV patients than in the remainder (p = 0.03). Response to chemotherapy (partial or minor response) was obtained more often in the patients with normal serum betaHCG than in those with serum betaHCG elevation (p = 0.03). We suppose that the ability to produce betaHCG is a rare but important biologic feature of lung carcinomas combined to some extent with chemoresistance.

[Typical and atypical pulmonary carcinoids--pathologic and clinical analysis of 77 cases]. / Typowe i atypowe rakowiaki pluc--patologiczna i kliniczna analiza 77 przypadków.

Neuroendocrine tumors of the lung represent a group of controversial pulmonary neoplasms regarding their classification, criteria for diagnosis, predictors of future behavior, and therapy. The histologic criteria for their classification rest heavily on the proposed by Arrigoni et al. in 1972, for atypical carcinoid (AC). According to these authors AC has mitoses between 5 and 10 per 10 high power fields (HPF), necrosis, hypercellularity and disorganized architecture. The survival analysis performed by Flieder et al. (1997) for a variety of clinical and histologic features revised the histologic criteria for separating AC from typical carcinoid (TC) and proposed a range of mitotic counts between 2 and 20 per HPF for AC. From 1978 until 1997, 77 resected pulmonary carcinoids were reclassified for TCs and ACs according to Flieder's et al. histologic criteria. The clinical and pathological various features were studied for the group of 62 TCs and 15 ACs. 77 patients (pts) entered the study: 29(38%) males and 48(62%)females; mean age 43 years, range 18-75 years, 46 pts underwent lobectomies, 16 bilobectomies, 12 pneumonectomies and 3 wedge resections. The patients with TC were younger than those with AC (males: 40 vs 50 years and females 42 vs 49 years). TCs were significantly smaller than ACs (mean diameter respectively: 24 mm vs 33 mm). Fifty four (87%) of TCs and all ACs had central localization. The time of patients observation ranged from 2 months to 18 and half years; 2 patients with TC died due to tumours progression; 3 due to other diseases. Regional lymph node metastases occurred in 10% TCs and 33% ACs (p = 0.032). The heterotopic bone formation appeared in 11(18%) TCs and 2(13%) ACs. The mitotic counts for AC range between 2 and 6 per 10 HPF, accompanied by small foci of necrosis in 2 cases. Peripheral carcinoids showed a spindle-cell morphology. The performed study has highlighted the new concept of the carcinoids classification and the importance of the mitotic counts as histologic criteria for AC diagnosis. The data based on the largest in Polish literature lung carcinoids collection.

Expression of CEA and trophoblastic cell markers by lung carcinoma in association with histological characteristics and serum marker levels.

The study of tumour markers in lung cancer has focused mainly on serum-based analysis. The controversy about carcinoembryonic antigen (CEA), pregnancy specific glycoprotein 1 (SP1) and beta human chorionic gonadotropin (betahCG) production in lung carcinoma has been reported in several studies. The aims of this study were: to explore an expression of CEA, SP1 and betahCG in various histological types of lung carcinoma with respect to the grade of differentiation; and to define the relationship between tumour marker expression and serum marker concentration. Ninety two lung tumours (75 non-small cell carcinomas (NSCLC) and 17 small cell lung carcinomas (SCLC)) entered the study. Tumour marker expression was compared with the serum levels of CEA, SP1 and betahCG in 57 patients (pts) with NSCLC and four pts with SCLC. Positive immunostaining of CEA and SP1 was observed in 87% NSCLC, and betahCG was found in 24% NSCLC. In the SCLC group positive staining showed in 29% of tumours, SP1 in 51% and betahCG in 18%. Positive CEA expression ranged from 50-100% within the carcinomatous cell population (pcp) and was more characteristic for well and moderately differentiated adenocarcinomas. This finding was in contrast to squamous cell carcinomas, where the majority of tumours expressed CEA in 1-50% pcp. A significant negative correlation was noticed for adenocarcinoma between tumour expression and grade of histological differentiation for CEA (P < 0.001) and SP1 (P = 0.023). Results were not significant for squamous carcinoma. Significant differences of serum CEA concentration were noticed between adenocarcinoma and squamous carcinoma (P = 0.003). In addition, a statistically significant relation was found between serum CEA concentration and an early (I + II) and advanced (IIIa + IIIb + IV) stage of NSCLC (P = 0.031). A significant correlation was noticed when serum CEA and tumour CEA expression was compared for NSCLC (P < 0.001), and for serum betahCG and tumour betahCG (P = 0.019).

Inhibition of angiogenesis by sulindac and its sulfone metabolite (FGN-1): a potential mechanism for their antineoplastic properties.

The nonsteroidal antiinflammatory drug sulindac (sulfoxide) is known to cause regression and prevent recurrence of adenomas in patients with familial adenomatous polyposis. The mechanism of action does not appear to require inhibition of prostaglandin synthesis since the sulfone metabolite of sulindac (FGN-1) retains the antineoplastic properties of sulindac but lacks inhibitory effects on cyclooxygenase, types 1 and 2. FGN-1 has been shown to induce apoptosis in a variety of tumor cell lines, and selective apoptosis of neoplastic cells has been proposed to account for its antineoplastic properties. Since angiogenesis is necessary for tumor progression and may be related to apoptosis, it is possible that inhibition of angiogenesis may also contribute to the antineoplastic properties of sulindac or FGN-1. In order to test this possibility, cells derived from several different types of human lung tumors were grafted intradermally in Balb/c mice. Sulindac sulfoxide and its sulfide and sulfone metabolites were administered for 3 days orally, in a daily dose of 0.025-0.5 mg, and angiogenesis was measured after 72 h using a previously described method. The results showed that sulindac sulfoxide and sulfone statistically inhibited angiogenesis.

[Coronary bypass grafting after failed percutaneous angioplasty (PTCA)]. / Pilne pomostowanie tetnic wiencowych po powiklanych angioplastykach wiencowych (PTCA).

Between January 1991 and September 1997, in the Cardiovascular Surgery Department of the Institute of Cardiology of Jagiellonian University Medical School, 23 patients underwent emergency CABG due to acute myocardial ischaemia in result of failed PTCA. Over the same period of time invasive cardiologists performed 1883 PTCAs out of which 23 (1.2%) were emergency cardiosurgical procedures, and in 38 patients, stents were implanted in the damaged coronary arteries. The patients' age ranged from 37 to 67 years (median 52.2). In all patients good left ventricular function was preserved, median ejection fraction being 64%. Two patients required IABP to support left ventricular function. 1-4 bypass grafts were implanted (median 1.9 per patient). In one patient, internal mammary artery was collected and then implanted into anterior interventricular branch. The most common complication was myocardial infarction which occurred in 12 patients (52%). In ten patients low output was observed postoperatively. One operated patient (a female died (4.3%). The mean time of hospitalization was 11 days. Emergency myocardial revascularisation procedures performed after failed PTCA, bring higher risk of mortality and dangerous postoperative complications.

[Early and late results of surgical treatment for bronchial carcinoids]. / Wczesne i odlegle wyniki leczenia chirurgicznego rakowiaków oskrzeli.

UNLABELLED: The aim of the study was to evaluate the efficacy and safety of surgical treatment of the bronchial carcinoids. Between 1983 and 1996 52 patients (pts) with typical carcinoid were operated. The group consisted of 23 males and 29 females aged from 20 to 68 years (mean 41.3 years). In the chest X-ray and CT scan round shadow were found in 21 (40.4%) cases, lung tissue atelectasis in 23 (44.1%) cases. The bronchial tree was normal in fiberoptic bronchoscopy in 8 cases. We performed 4 pneumonectomies, 3 wedge resection and 45 lobectomies (including 5 "sleeve" lobectomies). We haven't recorded any early post-op deaths. Only two pts (3.8%) developed post-op complications--cardiac arrhythmias. In two cases the surgical treatment was followed by radiotherapy for metastases in regional lymph nodes. The period of follow-up ranged from 3 to 166 months (mean 62.2 months). During that time we noticed the recurrence of tumor in 2 pts (3.8%). One patient died from cardiac reason. The 5-year survival among patients operated in the period 1983-1992 was 91.2%. The 10-year survival in the group of pts operated on between 1983 and 1987 was 90%. CONCLUSION: The surgical treatment of bronchial carcinoid is method of choice, very efficient and safe.

The incidence of malignancy in heart transplant recipients.

OBJECTIVES AND METHODS: 219 heart transplant recipients with survival over 3 months were retro- and prospectively analysed for the incidence of primary neoplasms. Patients received immunosuppressive drugs (cyclosporine A, azathioprine, steroids) with a 4-5 days induction course of Rabbit Anti-Thymocyte Immunoglobulin (RATG) or monoclonal antibodies induction /OKT3/ in some cases. Anti-rejection treatment consisted of pulse doses of methyloprednisolon or RATG. RESULTS: 9 cases of malignancy (4.1%) with one case of pre-malignant liver condition (dysplasia gigantocellulare, 0.45%) were found (8M; 1F; age: 45-67 y.o., x57.7). Symptoms of neoplasms occurred 7-79 months (x31.4) postoperatively. Skin carcinomas: planoepitheliale, spinocellulare, soft tissue neoplasms/mesenchymal sarcoma, larynx Ca planoepitheliale, lung: adenocarcinoma and Ca microcellulare, kidney Ca clarocellulare and post transplant non-Hodgkin lymphoma were diagnosed. Chemo- and radiotherapy, surgery and reduction of immunosuppression did not change the outcome of malignancy in 6 pts.; (regression-1 pt was., remission-2 pts). Patients died 7-86 months after Htx (x41), 4-25 mos. (x12.5) after suffering from first symptoms and 0-10 months (x4.9) after pathology-based diagnosis of neoplasm. CONCLUSIONS: Heart transplant recipients have an increased risk of carcinogenesis. The incidence of malignancies in the studied group is similar or even lower than in other reports.

Trophoblastic markers and CEA in non-small cell lung cancer: the comparison studies of tumour cells expression and serum concentration.

The study was designed to explore the tumour cell expression of three markers: hCG, SP1 and CEA in lung cancer in relationship with histological type and histological differentiation of tumours as well as serum concentration of antigens. 58 primary resected lung cancers: 28 adenocarcinomas, 27 squamous cell and 3 large cell carcinomas were included. Tumours immunoreactivity of three markers was evaluated by semiquantitative analysis. Simultaneously serum tumour markers were measured in 42 patients by enzyme radioimmunoassays. CEA and SP1 expressions in lung tumours were found in a majority of carcinomas-86% and 79% respectively. Expression of tumour markers was not associated with any certain histological type of carcinoma but was more characteristic for moderately and well differentiated adenocarcinomas. hCG positive tumour staining was less frequent than CEA and SP1 (only 22% tumours) and was much less intensive (5-50% population of carcinomatous cells) in the tumours. The study showed correlation between increased serum CEA concentration and tumour expression of antigen.

Prolidase activity and beta 1 integrin expression in moderately and poorly differentiated lung adenocarcinomas.

Primary human lung adenocarcinomas were divided into two groups according to the degree of histologic differentiation: G2-moderately and G3-poorly differentiated tumors. Each group was compared with normal lung tissue in respect to prolidase activity, its ability to interact with specific antibody, free proline and beta 1 integrin subunit content as well as ability of beta 1 integrin subunit to interact with specific antibody. It was found that prolidase activity in lung adenocarcinomas G3, was significantly elevated in comparison to normal lung tissue. In lung adenocarcinoma G2 no significant changes in the enzyme activity were observed. Increase in the enzyme activity was accompanied by increase of free proline content in the tissues. The western blot analysis revealed that prolidase of lung adenocarcinomas is identical to prolidase originated in control lung tissue. It was noticed that elevated activity of prolidase in adenocarcinomas G3 was accompanied by its high expression. In respect to beta 1 integrin expression, known to play an important role in metastasis, no difference was found between adenocarcinoma groups and the control lung tissue. The presented data suggest that the level of prolidase activity in lung adenocarcinoma may serve as a more sensitive marker for the histologic degree of malignancy, than the level of beta 1 integrin expression.