Plasmatic fibronectin in malignancies.

Plasmatic fibronectin has been studied in tumor patients on the basis of the role that unspecific opsonin may play in tumor growth and spreading. Alterations in fibronectin levels might be used as a biological marker and our purpose has been to evaluate the significance of this test in the biological diagnosis of cancer. When comparing the levels found in the control group (22.86 +/- 1.40 mg/dl) and in tumor patients (23.80 +/- 1.90 mg/dl), we observed no difference in the overall group. However, in relation to the localization of tumors, a significant increase was found in breast cancer (31.83 +/- 3.83 mg/dl) and a significant decrease in squamous cell carcinoma of the head and neck (9.56 +/- 1.68 mg/dl). These results suggest that plasmatic fibronectin could be useful as a biomarker in some types of tumors. Our conclusion was confirmed by analysis of ROC curves related to every one of the studied tumors.     

Oxidative protein damage in plasma of type 2 diabetic patients.

In this study, we evaluated protein oxidation in 84 patients with Type 2 diabetes with no complications and in 61 healthy volunteers who formed the control group, whose ages matched those of the patients. We determined plasma carbonyl and plasma thiol levels as markers of oxidative protein damage and erythrocyte glutathione, plasma ceruloplasmin and transferrin as markers of free radical scavengers. The concentrations (mean +/- SD) of both of plasma carbonyl (1.24 +/- 0.46 vs. 0.72 +/- 0.17 nmole/mg protein; p < 0.0001) and lipid hydroperoxides (1.8 +/- 0.63 vs. 1.3 +/- 0.21 micromole/l; p < 0.0001) were increased, and the concentration of plasma transferrin (3.85 +/- 0.65 vs. 4.59 +/- 0.79 g/l; p < 0.05) was decreased, respectively, in Type 2 diabetic patients compared with those of the controls. There were no significant differences in the concentrations of plasma thiol (0.0064 +/- 0.001 vs. 0.0068 +/- 0.001 micromole/mg protein), erythrocyte glutathione (2.54 +/- 0.57 vs. 2.65 +/- 0.56 mg/g Hb), plasma ceruloplasmin (548 +/- 107.30 vs. 609 +/- 93.34 mg/l) between the patients and the controls. These changes observed in diabetic patients contribute to the imbalance in the redox status of the plasma. We attribute this imbalance to oxidative protein damage in Type 2 diabetic patients clinically free of complications.     

Measurement of serum thyroxine binding prealbumin in various thyroidal states by radioimmunoassay

Serum thyroxine binding prealbumin (TBPA) levels in various thyroidal states were examined by radioimmunoassay (RIA). This technique is highly sensitive, accurate and reproducible. The normal mean (+/- 2SD) level of serum TBPA is 26.9 +/- 8.0 mg/dl (29.4 +/- 5.2 in men and 24.9 +/- 7.6 mg/dl in women). Serum TBPA levels in pregnant women were significantly lower than in normal females (P less than 0.05). Serum TBPA levels in patients with untreated hyperthyroidism were 12.9 +/- 4.0 mg/dl (mean +/- SD) and in patients with untreated hypothyroidism were 25.2 +/- 4.7 mg/dl (mean +/- SD). The mean TBPA concentrations in untreated hyperthyroidism were significantly lower than that for normal population (P less than 0.01), but untreated hypothyroidism was almost within normal range. The changes in TBPA levels in hyperthyroidism and hypothyroidism were similar to those in TBG levels. In untreated hyper- and hypothyroidism, restoration to euthyroidism by treatment was uniformly accompanied by a normalization of serum TBPA and TBG levels. A negative correlation between serum thyroid hormone binding protein (TBG and TBPA) and free thyroxine was observed in patients with hyperthyroidism. The coefficient of correlation between TBPA and free thyroxine was -0.80 (P less than 0.01) and between TBG and free thyroxine -0.58 (P less than 0.01). From these experiments it appears that not only TBG but also TBPA may play an important role in the regulation of the free thyroxine concentration in response to various thyroidal states.     

Renierol from marine sponge Haliclona.SP.: a natural inhibitor of xanthine oxidase with hypouricemic effects

The purpose of this study was to evaluate the inhibitory effect of renierol, extracted from marine sponge Halicdona.SP., on xanthine oxidase (XO) and its hypouricemic effect in vivo. Renierol and a positive control, allopurinol, were tested for their effects on XO activity by measuring the formation of uric acid and superoxide radical from xanthine. Renierol inhibited XO in a concentration-dependent and competitive manner. IC(50) value was 1.85 microg.ml(-1) through the measuring of uric acid and was 1.36 microg.ml(- 1) through the measuring of superoxide radical. Renierol was found to have an in vivo hypouricemic activity against potassium oxonate-induced hyperuricaemia in mice. After oral administration of renierol at doses of 10, 20 and 30 mg.kg(- 1), there was a significant decrease in the serum urate level (4.08 +/- 0.09 mg.dl(- 1), P < 0.01), (3.47 +/- 0.11 mg.dl(- 1), P < 0.01) and (3.12 +/- 0.08 mg.dl(- 1), P < 0.01), when compared to the hyperuricaemic control (6.74 +/- 0.23 mg.dl(- 1)). Renierol was a potent XO inhibitor with hypouricemic activity in mice.     

Effect of telmisartan on cholesterol levels in patients with hypertension - Saga Telmisartan Aggressive Research (STAR).

Saga Telmisartan Aggressive Research (STAR) is a single-arm, prospective multi-center trial to evaluate the effectiveness of treatment with telmisartan in patients with hypertension. A total of 197 patients with a systolic blood pressure of > or =140 or a diastolic blood pressure of > or =90 mmHg were enrolled in this study, and were prescribed 20 to 80 mg/day of telmisartan for 6 months. In all patients, both systolic and diastolic blood pressures decreased (159+/-20 to 135+/-12 mmHg, p<0.0001, 87+/-12 to 75+/-8 mmHg, p<0.0001, respectively). In addition, total cholesterol (TC) levels decreased from 200+/-40 to 188+/-33 mg/dl (p<0.05). In patients with TC > or =220 mg/dl, the change was more striking (249+/-33 to 204+/-31 mg/dl, p<0.0001). Even in patients receiving statins, TC levels still were decreased (216+/-51 to 190+/-31 mg/dl, p<0.02). In addition, TC levels were also decreased even in patients receiving telmisartan in exchange for other ARBs with TC > or =220 mg/d. Triglyceride (TG) levels were decreased (270+/-199 to 175+/-74 mg/dl, p<0.005) in patients with TG levels > or =150 mg/dl. Fasting blood glucose (FBG) was decreased (158+/-68 to 138+/-60 mg/dl, p<0.05) in patients with FBG > or =110 mg/dl. These results suggest that telmisartan may have favorable effects on lipid and glucose metabolism, in addition to lowering blood pressure. The profound effect of telmisartan to lower cholesterol suggests a potential use in hypertensive patients with dyslipidemia.     

How to express tumor markers in bronchoalveolar lavage

INTRODUCTION: Bronchoalveolar lavage (BAL) is a fundamental technique in the diagnosis of different respiratory diseases including lung cancer. Tumor marker values can be determined in the BAL fluid, but controversy still exists about how to express the results. OBJECTIVE: The aim of this study was to determine the best method of expressing tumor markers in BAL, either referring to total proteins or volume of fluid recovered. PATIENTS AND METHODS: A prospective, randomized, non-blind study was carried out. Seventy-six patients (72 men and 4 women) diagnosed with lung cancer and 17 subjects without respiratory disease were included. BAL was performed in all patients and the fluid retrieved was divided into two fractions: a bronchiolar fraction (F0) and an alveolar fraction (F1). Five tumor markers: cytokeratin fragment 19 (CYFRA 21-1), squamous cell carcinoma antigen (SCC), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and neuron-specific enolase (NSE) as well as total protein were measured in both fractions. The concentrations were expressed in relation to the volume of BAL fluid recovered (ng or mU/mL) and in milligrams of total protein of lavage fluid (ng or mU/mg TP). The SPSS 11.01 software was used for statistical analysis. Mann-Whitney U test and ROC curves were developed when significant differences were found. RESULTS: We found significant differences in the CYFRA 21-1 values in the two BAL fractions and in both ways of expressing its concentration; in SCC in F1 expressed in ng/mg TP; in TPA in F0 expressed in mU/mg TP; in TPS in both fractions expressed in mU/mg TP, and in NSE in both fractions in ng/mg TP. The markers that best differentiated tumors from controls (ROC curves) were CYFRA 21-1 in F0 and NSE in both fractions in ng/mg TP. CONCLUSIONS: Our study demonstrates that the concentrations of tumor markers in BAL expressed in relation to total protein were more effective than if expressed in mL of BAL fluid collected.     

Comparison of prolactin, CA 15-3 and TPA in breast carcinomas

Circulating prolactin, CA 15-3 and TPA were assayed pre-therapeutically and sequentially thereafter from 68 breast cancer patients attending the Gujarat Cancer and Research Institute, Ahmedabad--a regional cancer institute in Western India. The three marker values were correlated with the stage, histologic grade and disease status. At least one of the markers was elevated in 82% of patients. CA 15-3 and TPA levels were elevated with the advancement of stage. Prolactin levels were high in poorly differentiated tumors of pre-menopausal patients. The disease status was effectively reflected by the levels of prolactin and CA 15-3. TPA showed high false positivity so was of no use as an indicator of disease status. Recurrence could be predicted early, with a lead time of 3-6 months using prolactin and CA 15-3.     

Exercise-induced endotoxemia: the effect of ascorbic acid supplementation

Strenuous, long-duration aerobic exercise results in endotoxemia due to increased plasma levels of lipopolysaccharide (LPS) leading to cytokine release, oxidative stress, and altered gastrointestinal function. However, the effect of short-term strenuous aerobic exercise either with or without antioxidant supplementation on exercise-induced endotoxemia is unknown. A significant increase in the concentration of bacterial LPS (endotoxin) was noted in the venous circulation of healthy volunteers following maximal acute aerobic exercise (0.14(-1) pre-exercise vs. 0.24(-1) postexercise, p <0.01). Plasma nitrite concentration also increased with exercise (0.09 +/- 0.05 nM x ml(-1) vs. 0.14 +/- 0.01 nM x ml(-1), p <0.05) as did ascorbate free radical levels (0.02 +/- 0.001 vs. 0.03 +/- 0.002 arbitrary units, p <0.05). Oral ascorbic acid supplementation (1000 mg) significantly increased plasma ascorbic acid concentration (29.45 mM x l(-1) to 121.22 mM x l(-1), p <0.05), and was associated with a decrease in plasma LPS and nitrite concentration before and after exercise (LPS: 0.01(-1); nitrite: 0.02 +/- 0.02 nM x ml(-1) vs. 0.02 +/- 0.03 nM x ml(-1)). Ascorbic acid supplementation led to a significant increase in ascorbate free radical levels both before (0.04 +/- 0.01 arbitrary units) and after exercise (0.06 +/- 0.02 arbitrary units, p <0.05). In conclusion, strenuous short-term aerobic exercise results in significant increases in plasma LPS levels (endotoxemia) together with increases in markers of oxidative stress. Supplementation with ascorbic acid, however, abolished the increase in LPS and nitrite but led to a significant increase in the ascorbate radical in plasma. The amelioration of exercise-induced endotoxemia by antioxidant pretreatment implies that it is a free radical-mediated process while the use of the ascorbate radical as a marker of oxidative stress in supplemented systems is limited.     

Plasma transferrin levels in abnormal endocrine states. I. The changes in hypophysial diseases before and after treatment

The concentrations of plasma transferrin (Tf), which has been described possessing growth promoting activity in vitro, were determined in patients with hypophysial diseases before and after treatment. Plasma Tf levels in 74 healthy subjects were 269 +/- 3 (mean +/- SE) mg/dl. In 11 patients with active acromegaly, they were elevated to 353 +/- 11 mg/dl (P less than 0.001), while they were reduced to 168 +/- 14 mg/dl in 8 patients with hypopituitarism (P less than 0.001). They were normalized after appropriate treatment. These data indicate that plasma Tf varies according to endocrine status in relation to that of plasma somatomedin-C, and therefore its measurement may be useful clinically for the evaluation of the status of growth factors. However, the values should be assessed carefully in cases with proper Tf abnormalities, such as hematological, hepatic or renal disorders.     

Only a subset of 12-O-tetradecanoylphorbol-13-acetate-promoted mouse skin papillomas are promotable by benzoyl peroxide

The two-stage skin carcinogenesis model of initiation and promotion in Carcinogenesis-susceptible (Car-S) mice has been used to investigate the pathways of promotional activity of 12-O-tetradecanoylphorbol-13-acetate (TPA), a phorbol ester tumor promoter, and benzoyl peroxide (BzPo), a free radical-generating compound. To test whether distinct populations of 9,10-dimethyl-1,2-benzanthracene (DMBA)-initiated epidermal keratinocytes are responsive to the two promoters, tandem experiments were performed. DMBA-initiated Car-S mice were promoted twice weekly with maximal promoting doses of TPA or BzPo. When the number of papillomas/mouse reached a plateau, promotion in the TPA and BzPo groups was switched to BzPo or TPA, respectively, until achievement of a new plateau. Mice promoted with BzPo developed 11.0 +/- 1.3 papillomas/mouse and subsequent TPA promotion induced 13.8 additional papillomas, for a total of 24.8 +/- 2.1 papillomas/mouse. TPA-promoted mice developed 23.3 +/- 1.1 papillomas/mouse, and subsequent BzPo promotion for 91 days did not promote additional papillomas. Our results show a less than additive tumor response after sequential promotion with BzPo and TPA, or vice versa, indicating that the pathways of promotional activity of TPA and BzPo are interacting. While the final papilloma yield was similar at the end of the two tandem promotion experiments independently of promoter sequence, the percentage of mice developing carcinomas was significantly higher in mice that were promoted with BzPo in the first stage. No significant differences in the frequency and type of c-Ha-ras mutations were observed in TPA- and BzPo-promoted tumors, suggesting that promotion of DMBA-initiated cells by BzPo requires introduction of additional molecular alterations compared to TPA.     

The effect of growth hormone administration on lipids and lipoproteins in growth hormone-deficient patients

Plasma lipids, lipoproteins, and lipoprotein cholesterol levels were studied in a group (n = 8) of prepubertal growth hormone-deficient patients before and after growth hormone (GH) administration. Determination of plasma lipoproteins by a sensitive agarose gel electrophoretic technique demonstrated: (a) in the patients with two prebeta bands an intensification of the fast prebeta lipoprotein fraction after growth hormone administration; and (b) in the patients with one prebeta band the appearance of a second prebeta band after growth hormone administration. The mean (+/- SD) plasma triglyceride level before GH was 86 +/- 60 mg/dl and 158 +/- 95 mg/dl after GH (P less than 0.01). Mean (+/- SD) plasma cholesterol level before GH was 196 +/- 25 mg/dl and 174 +/- 28 mg/dl after GH (P less than 0.05). High-density lipoprotein cholesterol concentrations decreased significantly (P less than 0.001) from mean (+/- SD) 55 +/- 12 mg/dl before GH to 37 +/- 10 mg/dl after GH. Very-low-density lipoprotein cholesterol concentrations increased significantly (P less than 0.05) from mean (+/- SD) 13 +/- 12 mg/dl before GH to 23 +/- 15 mg/dl after GH. Low-density lipoprotein cholesterol concentrations decreased (N.S.) from mean (+/- SD) 123 +/- 15 mg/dl before GH to 114 +/- 15 mg/dl after GH. These lipid and lipoprotein changes could be mediated through the insulin antagonism, hyperinsulinemia, and a decrease in lipoprotein lipase activity caused by growth hormone.     

Association of low plasma high density lipoprotein (HDL)-cholesterol concentration with documented coronary artery disease in males with non-insulin dependent diabetes mellitus

Plasma lipid and lipoprotein concentrations were determined in 30 males without diabetes or symptomatic coronary artery disease (CAD), and compared to the values in age-matched and weight-matched males (n = 55) with non-insulin-dependent diabetes mellitus (NIDDM). Patients with NIDDM were further subdivided into those with (n = 30) and without (n =25) CAD. Mean (+/- SEM) plasma triglyceride concentrations were significantly increased (P less than 0.001) over control values (96 +/- 5 mg/dl) in patients with NIDDM, whether with (172 +/- 14 mg/dl) or without documented CAD (164 +/- 25 mg/dl). Plasma cholesterol concentrations were also higher (P less than 0.001) than normal (168 +/- 5 mg/dl) in both groups of patients with NIDDM (201 +/- 11 and 199 +/- 7 mg/dl, respectively, in patients with and without evidence of CAD). Plasma LDL-cholesterol concentrations were also greater (P less than 0.001) than normal (104 +/- 4 mg/dl) in patients with NIDDM, but were again similar in the group of diabetics (120 +/- 9 vs 128 +/- 6 mg/dl). However, plasma HDL-cholesterol concentrations were only reduced below control values in diabetes patients with CAD (30 +/- 1 mg/dl), whereas patients with NIDDM and no subjective evidence of CAD had HDL-cholesterol concentrations (37 +/- 3 mg/dl) which were similar to normal values (38 +/- 2 mg/dl). As a result, the ratio of LDL-cholesterol to HDL-cholesterol was highest in patients with NIDDM and CAD (4.2 +/- 0.3), lowest in the control population (2.8 +/- 0.2), and intermediate in those patients with NIDDM without subjective or objective evidence of CAD (3.6 +/- 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased reactive oxygen generation during H2O2 decomposition in the presence of samples from human rectal cancer

Reactive oxygen species (ROS) have generated a great deal of interest in the clinical field since experimental studies showed the involvement of these species in carcinogenesis. This paper reports the detection of ROS during the decomposition of H2O2 in the presence of samples obtained from tissues of 16 patients with rectal carcinoma (age 64 +/- 9 years) operated on in the Division of Surgical Oncology of Pomeranian Medical University, Szczecin (Poland). The samples were cut from the middle of the resected tumors and from the colonic mucosa (10 cm distant from the tumor and free of disease); they were processed and the supernatants, representing the soluble fraction, were used for measurements. Various methods for measuring free radical activity of the examined samples were used, such as chemiluminescence, fluorescent probe 2',7'-dichlorodihydrofluorescein, spin trap 5,5-dimethyl-pyrroline-1-oxide and EPR, the spectrophotometrically examined formation of diformazan during reduction of the p-nitroblue tetrazolium salt, and bleaching of p-nitrosodimethylalanine. A statistically significant difference (P < 0.001) was noticed in mean chemiluminescence +/- standard error of the mean in the presence of the tumor samples (42.6 +/- 7.3) in comparison to the control samples (234.6 +/- 36.0). Significantly decreased generation of ROS from the decomposition of H2O2 in the presence of the tumor samples in comparison to the control samples was also observed when the above-mentioned methods were used. Tumor samples had significantly lower superoxide dismutase activity (33 +/- 4 U/mg protein) than controls (93 +/- 14 U/mg, P < 0.001), which should contribute to a lower capacity of endogenous H2O2 production and therefore less ROS generation upon H2O2 decomposition. We conclude that the tested samples have different redox properties; this supports a possible role of ROS activity during carcinogenesis. Moreover, we propose a new, simple, and sensitive chemiluminescent method, which might be effective in sample differentiation.     

Preoperative CEA, NSE, SCC, TPA and CYFRA 21.1 serum levels as prognostic indicators in resected non-small cell lung cancer.

In 62 patients affected by resectable non-small cell lung cancer (NSCLC) submitted to radical surgery we evaluated the prognostic significance of CEA, NSE, SCC, TPA, and CYFRA 21.1 serum levels at diagnosis, as well as the predictive ability of these tumor markers with respect to histological type and pathological stage. The group was composed of 56 male and 6 female patients; the median age was 62 years (range 29-73 years). Thirty-four patients had a histological diagnosis of adenocarcinoma and 28 of squamous cell carcinoma; with regard to pathological stage, 32 patients had stage 1, 4 patients stage II and 23 patients stage IIIA disease. A good predictive ability with respect to histological type was obtained with SCC serum levels; as for pathological stage, TPA and CYFRA 21.1 were found to have moderate predictive ability. In this series of patients, at a median follow-up of 55 months after surgery, we found that both TPA and CYFRA 21.1 serum levels at diagnosis were reliable predictors of overall survival, high values of these markers being associated with a worse prognosis.     

Biochemical markers of endothelial dysfunction in patients with endocrine and essential hypertension

The aim of our study was to evaluate potential differences in the concentration of biochemical markers of endothelial dysfunction between essential hypertension, endocrine hypertension (pheochromocytoma, primary hyperaldosteronism) and control healthy group and to assess a potential relationship between these markers of endothelial dysfunction and vasopressor substances overproduced in endocrine hypertension. We have investigated 21 patients with moderate essential hypertension, 29 patients with primary hyperaldosteronism, 24 subjects with pheochromocytoma and 26 healthy volunteers. Following parameters of endothelial dysfunction were measured, von Willebrand factor (vWf), plasminogen activator (t-PA) and E-selectin (E-sel). Clinical blood pressure was measured according to the European Society of Hypertension recommendations. We found significantly higher levels of the von Willebrand factor in patients with essential hypertension in comparison with a control group (114+/-20 IU/dl vs 90+/-47 IU/dl; P=0.04) and patients with primary hyperaldosteronism (114+/-20 IU/dl vs 99+/-11 IU/dl; P=0.01). Patients with endocrine hypertension revealed increased levels of vWF compared to the control group, but these differences did not reach statistical significance. Levels of t-PA were increased in patients with pheochromocytoma in comparison with the control group (4.6+/-1.9 ng/ml vs 3.4+/-0.9 ng/ml; P=0.01) and with primary hyperaldosteronism (4.6+/-1.9 ng/ml vs 3.4+/-1.1 ng/ml; P<0.01). In case of E-selectin we found lower levels in patients with pheochromocytoma in comparison with other groups, but they differed significantly only with primary hyperaldosteronism (40.2+/-15.0 ng/ml vs 51.3+/-23.0 ng/ml; P=0.05). Our study did not reveal any convincing evidence of differences in the levels of biochemical markers of endothelial dysfunction between essential and endocrine hypertension. No correlation between the biochemical markers of endothelial dysfunction and vasopressor substances activated in endocrine hypertension was found.     

Relationship of tumoral hyaluronic acid and cathepsin D contents with histological type of gastric carcinoma

The aim of this work was to evaluate the cytosolic contents of hyaluronic acid (HA) and cathepsin D (CatD) in gastric carcinomas and their possible relationships with the clinicopathological parameters of the tumors. Our study demonstrated a wide variability in the cytosolic levels of HA (mean +/- SEM: 3748 +/- 411 ng/mg protein) and cathepsin D (52 +/- 4 pmol/mg protein) in the tumors of 78 gastric cancer patients. In addition, the tumoral contents of HA and CatD were significantly higher (p<0.005) in diffuse type (HA: 6027 +/- 1099 ng/mg protein; CatD: 75 +/- 13 pmol/mg protein) than in intestinal type (HA: 2735 +/- 242 ng/mg protein; CatD: 42 +/- 3 pmol/mg protein) carcinomas. These data suggest that both markers may contribute to the biological characterization of gastric carcinomas.     

Use of tumor markers in the management of head and neck cancer

Serologic tumor markers have been evaluated in the diagnosis, management and follow-up of patients with head and neck cancer. However, to the authors' knowledge no tumor marker has yet been shown to be useful for monitoring the response to chemotherapy in this type of disease, in particular for undifferentiated tumors. The pretreatment levels of CEA, TPA, SCC and ferritin were evaluated in 98 patients with advanced head and neck cancer. Of this group 64 patients were studied sequentially every month during planned chemotherapy and three weeks after treatment using standard commercial kits. The results showed the following sensitivity values: TPA 50%, CEA 36%, SCC 34% and ferritin 19%. The incidence and magnitude of the marker elevations were correlated with the extent of disease. In patients with squamous cell cancer SCC and CEA were elevated (by 68% and 54%, respectively) in tumors with good differentiation (G1), but only by 13% (both markers) in tumors classified as poorly differentiated (G3). CEA, SCC and ferritin serum levels were not correlated with response to chemotherapy, while TPA values correlated with the clinical response to treatment in 100% of patients with undifferentiated cancer and in 75% of those with squamous cell cancer. Our data indicate that in patients with head and neck cancer TPA appears to be a sensitive marker, followed in decreasing order of sensitivity by CEA, SCC and ferritin. However, SCC and CEA seem to be the most suitable markers for squamous cell cancer and in particular for more differentiated tumors (G1). Finally, TPA has proved to be a useful marker for monitoring the response to chemotherapy in patients with head and neck cancer, in particular for undifferentiated tumors.     

Tissue-type plasminogen activator (tPA) content in colorectal cancer and in surrounding mucosa: relationship with clinicopathologic parameters and prognostic significance

The aim of this study was to evaluate the cytosolic tissue-type plasminogen activator (tPA) content in colorectal cancer, its possible relationship with the clinicopathologic parameters of tumors, and its prognostic significance. We have therefore examined by immunoenzymatic assay the cytosolic tPA content in tumors and paired surrounding normal mucosa samples from 162 colorectal cancer patients. Cytosolic tPA levels were significantly higher in surrounding normal mucosa samples than in neoplastic tissues (4.01 +/- 5.07 vs 2.63 +/- 5.82 ng/mg protein; p < 0.0001). By contrast, no significant correlation was found between tPA content and clinicopathologic tumor parameters such as location, Dukes' stage, histologic grade, and DNA content or S-phase fraction. However, the results indicated that a high cytosolic tPA content (> 0.75 ng/mg protein) in tumors predicted for a shorter relapse-free and overall survival (both p < 0.05) in 123 resectable colorectal cancer patients who were prospectively evaluated during a mean follow-up period of 32.2 months. This suggests that tPA may give additional information to that provided by other biochemical markers currently used in colorectal cancer.     

The nuclear DNA content of human breast carcinoma. Associations with clinical stage, axillary lymph node status, estrogen receptor status and outcome

Using Feulgen-DNA cytophotometry, the nuclear DNA content was determined in specimens from 169 female patients with unilateral primary carcinoma of the breast. The tumors were classified as either diploid (73 cases: 43%) or hyperdiploid (96 cases), according to the ploidy of the tumor cells. Statistically significant associations were found between the DNA content and other characteristics of the patients and their tumors. (1) In postmenopausal women, inoperable tumors were more likely to be hyperdiploid (P less than .005). (2) In patients with operable disease, diploid tumors were less likely to have metastasized to the axillary lymph nodes (P less than .005) and were also less likely to have four or more positive nodes (P = .0044). (3) Overall, 71% of the diploid tumors and 52% of the hyperdiploid tumors were estrogen-receptor (ER) positive. This difference in proportions was statistically significant (P less than .05), but when the patients were divided into premenopausal and post-menopausal groups, the proportions of ER-positive tumors were not significantly different in either group. (4) In 113 patients considered suitable for studies on outcome (mean length of follow-up of 27 months, with a range from 0 to 71 months), the rates of relapse were 3 of 55 diploid cases and 17 of 58 hyperdiploid cases. The rate of relapse was higher in the hyperdiploid group, irrespective of lymph node status.     

Changes in plasma fibronectin levels in thyroid diseases

The plasma levels of fibronectin (Fn) have been measured in normal subjects and in patients with thyroid diseases. The mean plasma Fn levels in 62 normal adults was 32.0 +/- 6.0 mg/dl, whereas it was elevated to 62.6 +/- 16.1 mg/dl (mean +/- SD) in 25 patients with hyperthyroidism and decreased to 19.2 +/- 8.0 mg/dl in 9 patients with hypothyroidism. The 9 patients with simple goiter have normal values of 29.1 +/- 8.0 mg/dl. With the administration of anti-thyroid drugs, plasma Fn levels normalized, with a time lag, in parallel with normalization of the thyroid function. Positive correlation was obtained between Fn levels and serum levels of triiodothyronine (T3) and thyroxine (T4). The present findings indicate that measurement of plasma Fn both in the basal state and during treatment provides evidence of altered Fn metabolism in thyroid diseases and serves to follow up the effect of treatment.