Combined use of haemostatic system indices for evaluation of upper respiratory tract cancer progression.

AIM: To analyze whether comprehensive assessment of haemostatic system components, in particular, indices of coagulation and fibrinolytic systems along with functionally related proteins, could be indicative of upper respiratory tract (URT) cancer progression. MATERIALS AND METHODS: Indices of coagulation and fibrinolytic systems along with functionally related proteins, in particular, trypsin-like amidolytic activity, trypsin-like proteolytic activity, thrombin-like amidolytic activity, elastase-like amidolytic activity, fibrinolytic activity, potential amidolytic plasmin activity, content of fibrinogen, antithrombin III, α1-proteinase inhibitor, and α2-macroglobulin, and prothrombin time were evaluated in blood plasma of patients with URT cancer of II (n = 10) and III (n = 25) stages with the use of routine biochemical methods. RESULTS: For both groups of patients with URT cancer there have been shown notable differences for the majority of the studied indices, especially the indexes of proteolytic activities, from these of healthy donors, and in the case of URT cancer of III stage they reached statistical significance. In contrary, the changes in the content of antithrombin III, α1-proteinase inhibitor, and α2-macroglobulin were insignificant. In both groups of patients significant increase of fibrinogen content has been registered, while the content of soluble fibrinogen didn't change. Also, in both groups of patients there a significant increase of potential activity of plasminogen was documented, while clot lysis time was significantly increased only in patients with III stage URT cancer. Multifactorial analysis of haemostatic system indices evidenced for efficacy of their combined use for evaluation of URT cancer progression risk. CONCLUSION: Combined use of fibrinogen and α2-macroglobulin content and the level of amidolytic thrombin-like activity could serve as an indicator of URT cancer progression.

Is determination of matrix metalloproteinases and their tissue inhibitors serum concentrations useful in patients with gastroenteropancreatic and bronchopulmonary neuroendocrine neoplasms?

INTRODUCTION: Gastroenteropancreatic (GEP) and bronchopulmonary (BP) neurendocrine neoplasms (NENs) are rare and slowly growing tumours. Matrix metalloproteinases (MMPs) degrade extracellular matrix and are responsible for invasion and metastasis. Tissue inhibitors of matrix metalloproteinases (TIMPs) affect the invasiveness of tumour cells and the formation of distant metastases. The aim of this study was to evaluate selected MMPs (MMP2 and MMP9) and their tissue inhibitors (TIMP1 and TIMP2) depending on the pTNM classification, grading, and the occurrence of metastases. MATERIAL AND METHODS: The study group consisted of 86 patients with GEP NENs. The control group consisted of 31 healthy volunteers. Serum levels of TIMP1, TIMP2, MMP2 and MMP9 were determined by ELISA (R&D Systems) in all the study subjects. The statistical calculations were performed using MedCalc. RESULTS: We observed significant differences in MMP2 and TIMP1 levels between the study group with NENs and the control group. TIMP1 levels were significantly higher in patients with high-grade NEN (NEC, neuroendocrine carcinoma) compared to patients with low-grade tumour (NET G1, neuroendocrine tumours G1) (p 〈 0.017). We also observed a significant correlation between TIMP1 levels and the presence of metastases in the group of patients with GEP NENs, and also higher TIMP1 levels than those in the patients without metastases (p 〈 0.05). We also found a higher likelihood of metastases in patients with GEP NENs with TIMP1 levels exceeding 206.4 ng/mL. CONCLUSIONS: Patients with NENs secreted larger quantities of MMP2 and TIMP1. TIMP1 may be considered a marker of metastases in patients with GEP NENs.

Cytokine pattern in Kaposi's sarcoma associated with immune restoration disease in HIV and tuberculosis co-infected patients.

We analysed the evolution of different cytokines (IL-4, IL-6, tumour necrosis factor alpha and vascular endothelial growth factor; VEGF) involved in the development of Kaposi's sarcoma in two patients in whom HIV infection presented with disseminated Mycobacterium tuberculosis infection. They simultaneously developed tuberculosis-associated immune restoration disease and Kaposi's sarcoma shortly after the initiation of HAART. Analysis of VEGF and pro-inflammatory cytokines led us to hypothesize that Kaposi's sarcoma could be promoted by the tuberculosis immune response.

Selenoprotein P in plasma in relation to cancer morbidity in middle-aged Swedish men.

The premorbid level of selenoprotein P in plasma from subjects with cancer at different sites was compared with that from control subjects in a nested case-control study. A health screening of 12,500 middle-aged men was performed during 1974-1982 in Malmö, Sweden, and from the 400 cancer cases that were identified during follow-up until the end of 1988, 302 plasma samples were available for analysis of selenoprotein P. Two living controls per case of the same screening day and age were chosen. Selenoprotein P levels in subgroups of major cancer sites were lower in cases than in controls for the respiratory tract (1.20 and 1.30 arbitrary units, respectively; p < 0.05) cancer group. The odds ratio for overall cancer risk in the lowest quintile of selenoprotein P level compared with that in the highest was 5.2 [p (for trend) = 0.01]. In subgroups of major cancer sites, the odds ratios for cancer risk in the lowest tertile compared with the highest were 6.0 [p (for trend) = 0.004] in the respiratory tract and 3.4 [p (for trend) = 0.002] in the digestive tract. In cases + controls, selenoprotein P was lower in smokers than in nonsmokers (p < 0.05). Selenoprotein P was significantly correlated to plasma albumin, fasting blood glucose, and body mass index and inversely correlated to plasma alpha 1-antitrypsin and gamma-glutamyl transferase. The results suggest that a low plasma selenoprotein P level is associated with higher future risk of respiratory and digestive tract cancer in middle-aged men.

Serum copper and zinc concentrations in serum from patients with cancer and cardiovascular disease.

A single cross-sectional study for serum copper and zinc levels was evaluated in 20 patients with cancer (respiratory, digestive, haematological, gynaecological) and 21 patients with cardiopathy (acute myocardial infarction and ischemic cardiomyopathy). A control group of 84 healthy subjects was selected. The mean serum zinc levels in patients with gynaecological cancer and ischemic cardiomyopathy were significantly lower than the control group (P < 0.05). However, the mean serum copper level was not statistically different among patients with cancer (P < 0.05) and cardiomyopathy (P > 0.05) than the control group. Male patients did not have statistically different values for serum Cu (P > 0.05) and Zn (P < 0.05) than those found in female patients. Patients' age did not have any statistical influence (P > 0.05) on serum Cu and Zn levels.

Serum YKL-40: a new potential marker of prognosis and location of metastases of patients with recurrent breast cancer.

YKL-40 is a recently discovered glycoprotein which is related in amino acid sequence to the chitinase protein family, but has no chitinase activity. Although the function of YKL-40 is presently unknown, the pattern of its expression by some tissues suggests that YKL-40 could function in tissue remodelling. The diagnostic features and relation to survival of serum YKL-40 have not been examined previously in human malignancies. In the present study YKL-40 was measured in serum obtained from 60 patients at the time that breast cancer recurrence was suspected. The median serum YKL-40 in patients with visceral or bone metastases was 328 and 157 micrograms/l, respectively and significantly higher compared to controls (99 micrograms/l, P < 0.001). Kaplan-Meier survival curves demonstrated that survival rates after 18 months were 24% for patients with high serum YKL-40 (> 207 micrograms/l = the 95 percentile of controls) and 60% for patients with normal serum YKL-40. The significance of the difference between the shorter survival of patients with high serum YKL-40 and the longer survival of patients with normal serum YKL-40 was high (P < 0.0009). When evaluated with other prognostic factors of survival after recurrence of breast cancer, serum YKL-40 and serum lactate dehydrogenase (LDH) were the most significant independent factors. The results indicate that determination of serum YKL-40 can be used as a prognostic marker related to the extent of disease and survival of patients with recurrence of breast cancer. In addition, the serum YKL-40 level may be of value in the follow-up of patients with breast cancer and in evaluating potential metastatic spread.

Carcinoembryonic antigen in staging and follow-up of patients with solid tumors.

The presence of a tumor antigen in human colonic carcinomas and their metastases was described about 25 years ago. This antigen, called carcinoembryonic antigen (CEA), is one of the first known tumor markers. Since then, many more have been described, but CEA, determined alone or in combination with others, is still one of the most used. CEA is not organ specific and abnormal values may be found in a wide range of carcinomas, especially those with gastrointestinal involvement. CEA assay should not be used for cancer diagnosis because its sensitivity in patients without cancer metastases is low. In addition, abnormal CEA values may be found in patients with benign diseases. However, the probability of malignancy increases directly with CEA concentration. Its main clinical applications are prognosis, early diagnosis of recurrence and follow-up of patients with carcinomas. In a wide range of malignancies, CEA serum levels are clearly related to tumor stage. Presurgical CEA serum levels are a well-established prognostic factor in colorectal, breast and lung cancer. Patients presenting with increased preoperative CEA serum levels have both a shorter disease-free interval and lower survival than those with normal CEA levels. In the early diagnosis of recurrence, CEA also plays an important role: in about 70-85% of patients with colorectal tumors and in 40-50% with breast cancer, CEA serial increase is the first sign of tumor recurrence. In patients with disseminated tumors, serial determinations are also a useful tool for therapy monitoring: CEA values decrease with effective treatment while stable or increasing values are observed when treatment is not effective.

Oncoproteins as biomarkers of a preclinical form of cancer of the respiratory tract induced by environmental carcinogens.

Experimental data and clinical observations indicate that an increased expression of oncogenes or their point mutations play an essential role in the process of carcinogenesis. It was important to find out that environmental and occupational carcinogens activate cellular oncogenes and contribute to increased amounts or occurrence of mutated oncoproteins. The latter are responsible for activating mechanisms which further the neoplastic transformation of cells. The researches are mainly concerned about two oncoproteins: oncoprotein coded by the ras oncogene--called p21 protein and oncoprotein coded by the erbB-2 oncogene--called p185 protein. Investigations performed on neoplastic cells show that the neoplastic transformation process involves not only the afore-said oncogenes and their oncoproteins but also other oncogenes, and that the process itself required activating of more than one oncogene. At present, it is possible to use measurements of oncoproteins in the biological material which is easily available. Due to this fact, a number of works in which measurements of oncoproteins in blood serum were used to assess cancer risk in persons exposed to carcinogens present at the work place, have been published.

Distribution and reproducibility of aryl hydrocarbon hydroxylase inducibility in a prospective population study of middle-aged male smokers and nonsmokers.

Aryl hydrocarbon hydroxylase (AHH) inducibility was determined in a lymphoblast test system in 2,000 consecutive middle-aged male smokers, 304 ex-smokers, and 218 never-smokers in the same birth-year cohorts. Intraindividual, intraobserver, and interobserver, as well as temporal, reproducibility was checked in a special double-blind quadruplet sample series from 20 other consecutive middle-aged men. The results showed a three-modal phenotype distribution of AHH inducibility with high (fold induction greater than or equal to 3.6), intermediate (2.6-3.6) and low (less than or equal to 2.5) levels ranging between 7.6% to 10.5%, 38.5% to 43.0%, and 46.5% to 53.9%, respectively, in all the smoking categories. The reproducibility of the measurements was excellent, with one-way variance in the order of 0.007 to 0.033, and the applied assay method can therefore be used in large-scale prospective population investigations. Such are required in order to establish a cause-effect association between high AHH inducibility and smoking-related malignancies of the respiratory tract and oral cavity, as has been suggested from earlier retrospective studies in more limited clinical materials of cancers and precanceroses of these varieties.

[Changes in the serum protein profile during radiotherapy of the upper respiratory and digestive tracts]. / Evolution du profil protéique sérique au cours de la radiothérapie des voies aéro-digestives supérieures.

Patients with a cancer of the upper airways or upper gastro-intestinal tract present a state of malnutrition as a result of the disease itself and, more importantly, as a result of its localisation. Loco-regional radiotherapy often leads to an aggravation of this state. The protein profile, consisting of nine serum proteins, was determined each week in 54 patients with cancer of the upper respirato-gastro-intestinal tract receiving radiotherapy. During the course of radiotherapy, the already altered nutritional state of these patients deteriorated further, as shown by a regular and significant downturn in the weight curve. The weekly monitoring of the protein profile showed a gradual and significant decrease in the levels of nutritional proteins (prealbumin, retinol binding protein, transferrin) and immunoglobulins (IgM, IgA) and a small variation in the levels of inflammatory proteins (haptoglobin, orosomucoid, C3 complement fraction, alpha 1-antitrypsin). The protein profile, established on the basis of carefully selected proteins, can provide useful information in the monitoring of a patient's nutritional state.

Abnormal bone and parathyroid histology in carcinoma patients with pseudohyperparathyroidism.

Postmortem bone and parathyroid gland histology in nine hypercalcemic cancer patients without bone metastases was compared to bone and parathyroid histology in ten normocalcemia patients. Parameters of parathyroid function, including serum immunoreactive parathyroid hormone, acid base status, serum phosphate, and nephrogenous cyclic AMP were measured in the hypercalcemic group and compared to normals and to patients with primary hyperparathyroidism. Bone histology in all nine hypercalcemic cancer patients showed increased osteoclastic bone resorption and increased fibrous connective tissue in the bone marrow. Parathyroid glands were of normal size in all nine patients but contained little or no fat, one criterion of parathyroid hyperplasia. In the normocalcemic cancer patients only 2/10 had minimally increased bone resorption while 7/10 had decreased or absent stromal fat in the parathyroid glands. Despite the hyperplastic appearance of the parathyroid glands, serum biochemical parameters in the hypercalcemic cancer patients indicate a state of suppressed parathyroid function suggesting that the osteoclastic bone resorption is related to a humoral substance elaborated by the tumors which is distinct from parathyroid hormone.

The serum levels of some trace and bulk elements in cancer patients.

The levels of copper, zinc, calcium, manganese and magnesium have been monitored in the sera of patients suffering from various types of cancer. Only serum copper appeared to be of any diagnostic significance, its levels being above the normal reported range in the breast cancer, leukaemia and Hodgkin's lymphoma patients. In the case of breast cancer, serum copper is progressively elevated according to the stage of the disease. Serum calcium levels were also significantly lower in patients with tumours of the breast, gastrointestinal tract and cervix. The results suggest that serum copper levels could be of prognostic significance in breast cancer patients receiving radiotherapy.

[Quantitative immunoenzyme method of analyzing embryonal prealbumin (EPA-1) in biological fluids]. / Kolichestvennyi immunofermentnyi metod opredeleniia émbrional'nogo preal'bumina (EPA-1) v biologicheskikh zhidkostiakh.

A quantitative immunoenzymatic method (ELISA) has been developed for detection of embryonic prealbumin (EPA-1). This method allows EPA-1 to be detected in human serum in an amount of 4 to 100 ng/ml. The high levels of EPA-1 (over 4 ng/ml) were observed in all cases (27 patients) of tumors of connective tissues, in 50 of 51 in brain tumors, in 39 of 341 in gastrointestinal tract tumors, in 4 of 13 in breast tumors, and in 21 of 51 tumors of the respiratory tract. The levels of EPA-1 in donors and pregnant woman sera normally did not exceed 4 ng/ml. However, about 3% of the samples of these sera had the levels of EPA-1 from 4 to 12 ng/ml.

Usefulness of serial carcinoembryonic antigen (CEA) determinations in monitoring chemotherapy.

Serial carcinoembryonic antigen (CEA) levels were measured during chemotherapy for metastatic cancer in 94 patients. Criteria for chemotherapy responses were those used by the Central Oncology Group. Patients were classified according to changes in CEA levels and response to chemotherapy. Four categories represented a positive correlation: (1) increasing abnormal CEA with progressing disease, (2) decreasing abnormal CEA with disease regression, (3) unchanged abnormal CEA with stable disease, (4) change from normal to abnormal CEA with progressive disease. Positive correlation of serial CEA levels with clinical responses occurred in 71% of patients with GI cancer, 51% with breast cancer, 42% with sarcoma, 50% with respiratory cancer, and 25% with melanoma. These data indicate that serial CEA determinations may be of value as an additional parameter of response to chemotherapy in gastrointestinal cancer.

[Study on the relationship between serum alpha 1 antitrypsin level, the phenotype Pi and various bronchopulmonary diseases]. / Recherche de liaisons entre le taux sérique d'alpha-1-antitrypsine, le phénotype P1 et différentes affections broncho-pulmonaires

The authors determined in 418 adults, males and females, admitted to hospital on the Respiratory Unit of the Montpellier University Hospital, the serum levels of alpha-1-antitrypsin, phenotype Pi and serum immunoglobulin levels. They compare these data together and with the diagnosis using a mathematical method known as factorial correspondence analysis.