Pro-Gastrin-Releasing Peptide as a Marker of Small Cell Lung Cancer.

The serum levels of pro-gastrin-releasing peptide (proGRP), neuron-specific enolase (NSE), and chromogranin A (CgA) were studied in 69 patients with small cell lung cancer and 50 apparently healthy donors. A significant increase of all studied biochemical markers was revealed in small cell lung cancer patients, while the highest diagnostic efficiency was demonstrated by proGRP compared to NSE and CgA. ProGRP is a promising biochemical marker of small cell lung cancer, especially sensitive in patients with distant metastases (in the brain, liver, and bones).

Assessment of iron metabolism disorders and adequate treatment of anemic syndrome in patients with breast cancer on the background of adjuvant chemotherapy.

Early and adequate correction of the anemic syndrome (AS) of cancer patients can prevent deterioration in the quality of life and be considered as a reserve for increasing the effectiveness of treatment for breast cancer (BC). The aim of the study was to assess the status of iron using modern methods of ferrokinetics in breast cancer patients on the background of adjuvant chemotherapy for early diagnosis and adequate treatment of AS. The object of the study included 21 breast cancer patients with a relatively favorable prognosis, with luminal types A and B (Her 2 / neu positive or negative), three times negative type. The examination was carried out in the postoperative period, against the background of adjuvant chemotherapy. The main metabolites of ferrokinetics were studied: hepcidin 25 (GP25); ferritin (FR); soluble transferrin receptors (rRTP); transferin (TRF); iron (Fe); erythropoietin (EPO); CRP and IL-6 indicators. AC correction was performed (ferinject, epotin-alpha, B12). 10 (47.6%) patients with breast cancer had AS. Most of them were diagnosed with IDA with microcytic, hypochromic characteristics of erythrocytes, low concentration of FR, Fe, GP25, IL-6, CRP, and high levels of TRP and rRTP. Functional iron deficiency (FDF) was established in some patients. In contrast to patients with IDA, they had a high concentration of FR, CRP and significant production of GP25, IL-6. The EPO level was not optimal for the majority of patients with AS. In isolated cases, during treatment with recombinant erythropoietins, a deficiency of vitamin B12 (cyanocobalamin) was revealed. The rational use of iron preparations, vitamins, and recombinant forms of EPO made it possible to restore Fe metabolism, stabilize the hemoglobin level, and also improve the condition of most breast cancer patients. The obtained data on IL-6, GP25, CRP indicate a certain relationship between them in the development of anemia with VDF in breast cancer patients and the need for further study of the characteristics of iron metabolism in cancer patients.

The role of interleukin-6 and hepcidin 25 in the pathogenesis of anemic syndrome associated with malignant neoplasms with breast cancer patients before neoadjuvant chemotherapy.

A study of interleukin-6 (IL-6), hepcidin-25 (GP-25) was conducted in 22 patients with breast cancer before neoadjuvant chemotherapy and in 27 healthy women in the control group. Significant expression of the GP-25 protein was revealed in breast cancer patients, compared to control. The rates were high both in patients with anemic sindrome (AS) and without it (p <0.01). Latent iron deficiency, AS, IDA and functional iron deficiency (FJ) were more often detected in patients with stage III disease. A significant difference in the parameters of GP-25 and IL-6 was noted, the indicators were higher in patients with stage III (p <0.01). No close correlation was found between IL-6, GP-25 and other acute-phase proteins (FR, CRP) at the initial stages of AS formation. On the contrary, a positive correlation was observed in patients with IDA and FJ between IL-6 and all acute-phase proteins (GP-25, FR, CRP). However, a small number of observations do not allow an unambiguous conclusion about the role of IL-6 and GP-25 expression in the development of AS in cancer patients with breast cancer and requires further study.

Glial Fibrillary Acidic Protein in the Diagnosis and Prognosis of Malignant Glial Tumors.

Serum levels of glial fibrillar acidic protein (GFAP) were analyzed in 317 patients with primary and metastatic tumors of the brain, 78 patients with neurological diseases, and 66 normal subjects. A significant increase in the basal level of GFAP was typical of patients with glioblastomas in comparison with other groups (patients with astrocytomas, cerebral metastases, benign tumors, non-tumor diseases, and healthy subjects). An association of GFAP levels with unfavorable prognosis of overall survival in patients with glioblastoma was revealed. The data attest to high specificity and sensitivity of GFAP as a biochemical marker of glioblastoma.

[Development of strategic approaches to modern diagnosis of anemic syndrome in patients with breast cancer.]

A study of the clinical analysis of blood and major metabolites of ferrokinetics in 107 breast cancer patients before treatment was conducted. In 31 (28.9%) patients revealed anemic syndrome (AS). A feature of the AS is pronounced microcytosis, erythrocyte hypochromia and low hemoglobin content in reticulocytes. Most often (n = 22; 71%) there was iron deficiency (IDA), which was characterized by a low concentration of iron (F), ferritin (FR), hepcidin 25 (GP25), interleukin-6 (IL-6) and high - soluble transferrin receptors (rTFR), transferrin (TRF). In 9 (29%) patients with AS, on the basis of a high concentration of FR, GP25, IL-6, the anemia of chronic disease (AHZ) with functional iron deficiency (FDI) was established. In 23 (74.2%) patients with AS, the was a deficiency of erythropoietin (EPO), the lowest rates were found in the group of patients with a common tumor process and FDI, with less in patients with IDA.

Immunochemical Diagnosis of Multiple Myeloma.

The diagnostic potentialities of complex immunochemical analysis of the serum and daily urine were evaluated in 118 patients with multiple myeloma. In 95 patients, we observed secretion of monoclonal intact immunoglobulins with heavy chains G (N=69), A (N=19), and M (N=4) and biclonal secretion of paraproteins G and A (N=3). Bence-Jones protein was detected in the sera and daily urine of 16 patients and Bence-Jones proteinuria alone was detected in 3 patients. The diagnostic sensitivity of serum immunoelectrophoresis in multiple myeloma is 94.1%. Analysis of paraproteinuria is particularly important in Bence-Jones myeloma, when paraprotein excretion may be not associated with paraproteinemia. Complex study by immunoelectrophoretic and immunoturbidimetric methods in multiple myeloma increases the diagnostic sensitivity to 99.2%.

Free Immunoglobulin Light Chains as Criteria of Extracorporeal Hemocorrection in Patients with Monoclonal Gammopathies.

Elimination of free immunoglobulin light chains with the use of EMic2 selective filters was carried out in 12 patients with monoclonal gammopathies and high production of free immunoglobulin light chains. We showed that extracorporeal detoxification for direct removal of excessive free immunoglobulin light chains from the circulation is advisable for these patients, irrespective of the presence and severity of renal insufficiency. Rapid reduction or elimination of free light chains of immunoglobulins in the course of selective extracorporeal elimination helps to prevent the development of irreversible renal failure and to perform adequate antitumor therapy.

Chromogranin As a Biochemical Marker of Neuroendocrine Tumors.

Comparative study of plasma chromogranin A levels was carried out in 227 patients with neuroendocrine tumors of various locations and 66 normal subjects, men and women, by standard ELISA. In patients with tumors of all locations (pancreas, stomach, small and large intestine, and lungs), the glycoprotein levels were significantly (p<0.000001) higher than in controls. The patients demonstrated high variability of chromogranin A levels; the maximum concentrations were detected in patients with neuroendocrine tumors of the stomach and lung. The highest median values of chromogranin A were found in patients with tumors of the small intestine, large intestine, and pancreas. A relationship between secretion of chromogranin A and dissemination and activity of the neuroendocrine tumor was detected, which was the maximum in patients with metastases in the liver and carcinoid syndrome. High diagnostic sensitivity of chromogranin A was shown: 85.8% for the total group of patients; specificity was 98.5%. These data confirmed high efficiency of chromogranin A as the marker of neuroendocrine tumors. Detection of this marker promotes more accurate diagnosis and evaluation of dissemination of the neuroendocrine tumors.

[The glio-fibrillar acid protein in blood serum of patients with brain tumors and neurological diseases of non-tumorous etiology].

The glio-fibrillar acid protein is considered as a biomarker of astroglyal pathology in case of neurological diseases. The glio-fibrillar acidprotein is intracytoplasmatic filamentous protein specific for cellular skeleton of mature astrocytes playing important role in their differentiation. According publications' data, the highest serum concentrations of glio-fibrillar acid protein are detected in case of neurolepsia, meningitis, febrile schizophrenia, encephalitis, Alzheimer's disease, multiple sclerosis, stroke, opened cranial-cerebral injury and other critical conditions related to damage of hematoencephalic barrier. In the recent years, publications appeared considering analysis of glio-fibrillar acid protein in blood of patients with primary and metastatic brain tumors. Purpose of study To compare levels of glio-fibrillar acid protein in blood serum of patients with primary and metastatic brain tumors and also patients with neurological diseases of non-tumorous etiology and healthy individuals. Material and methods. The analysis was applied to levels of glio-fibrillar acid protein in blood serum of neurooncologic patients (n=175) and also patients with pathology of brain of non-tumorous etiology i.e. degenerate and cerebrovascular diseases (n=38). The control group consisted of 52 healthy individuals with no principal differences in gender and age from examined groups of patients. The concentration of glio-fibrillar acid protein was established in blood serum using immune enzyme analysis in reagents of "BioVendor" firm. Results and discussion. The analysis of results of detection of glio-fibrillar acid protein demonstrated that in patients with primary malignant brain tumors the initial levels of marker were reliably higher than compared with groups of healthy individuals, patients with benign neoplasms, patients with cerebral metastases, and also in case of non-tumorous pathology. The levels of glio-fibrillar acid protein achieve their maximum in case of glioblastoma. The obtained results permit assuming existence of relationship between increasing of content of glio-fibrillar acid protein in blood serum and damage of hematoencephalic barrier permeability in case of development of malignant neoplasms of brain. Conclusion. The obtained data testify higher specificity and sensitivity of glio-fibrillar acid protein as a biochemical marker of glioblastoma appropriate to be applied in case of primary examination of patients with brain affection.

[The diagnostic significance of biochemical markers.]

INTRODUCTION: The modern diagnostic of neuroendocrine tumors is based on analysis of compounds produced by tumor cells (peptides, amines, hormones). PURPOSE OF STUDY: To evaluate diagnostic effectiveness of Chromogranin A, serotonin and its metabolite 5-hydroxyindolilacetic acid as biochemical markers of neuroendocrine tumors as biochemical markers of neuroendocrine tumors. MATERIAL AND METHODS: The detection of Chromogranin A and serotonin in blood serum and 5-hydroxyindolilacetic acid in day urine was applied to 330 patients with neuroendocrine tumors of lungs, pancreas, stomach, small and large intestines and also to 115 healthy males and females. The detection was implemented by enzyme-linked immunosorbent assay based on testsystems "Chromogranin A ELISA Kit" (Dako A/S, Denmark), "Serotonin ELISA" and 5-HIAA ELISA (IBL International GMBH, Germany). RESULTS AND DISCUSSION: The levels of Chromogranin A at all localizations of neuroendocrine tumors reliably (p<0.000001) exceeded corresponding control index. In case of serotonin and 5-hydroxyindolilacetic acid reliable differences were established in all groups except neuroendocrine tumors of stomach. The dependence is established between secretion of markers from prevalence and activity of neuroendocrine tumors. The corresponding levels were higher in patients with metastases in liver and under carcinoid syndrome as compared with patients without corresponding clinical manifestations. The evaluation of diagnostic significance of Chromogranin A, serotonin and 5-hydroxyindolilacetic acid was applied considering threshold levels calculated according results of their detection in control group (33 ng/ml, 320 ng/ml and 60 mkmol/day correspondingly). The high diagnostic sensitivity of Chromogranin A was demonstrated that amounted to 80.6% at specificity 98.5% on the whole in group of patients with neuroendocrine tumors. The serotonin and 5-hydroxyindolilacetic acid manifested comparable diagnostic sensitivity only in patients with carcinoid syndrome (72.5 and 60.3%). CONCLUSION: The obtained data substantiate high effectiveness of Chromogranin A as a marker of neuroendocrine tumors. The detection of this marker contributes into enhancement of accuracy of diagnostic and evaluation of prevalence of tumors of neuroendocrine nature. The serotonin and 5-hydroxyindolilacetic acid are markers of carcinoid syndrome.

Biochemical markers of bone metabolism in breast cancer.

The relationship between biochemical markers of bone resorption (C-terminal telopeptide, deoxypyridinoline, tartrate-resistant acid phosphatase 5b) and osteosynthesis (bone alkaline phosphatase) and clinical manifestations of bone metastases were studied in 239 patients with breast cancer with and without signs of bone involvement. High levels of C-terminal telopeptide and bone alkaline phosphatase were associated with poor prognosis: more severe skeletal complications and lesser survival values. These biochemical markers can be used for prognosis and optimization of therapy for bone metastases in patients with breast cancer.

Components of the RANK/RANKL/OPG system, IL-6, IL-8, IL-16, MMP-2, and calcitonin in the sera of patients with bone tumors.

Serum levels of sRANKL, RANK, OPG, IL-8, IL-6, IL-16, MMP-2, and calcitonin were measured by ELISA in patients with malignant, borderline, and benign bone tumors and in healthy individuals (control). Serum levels of RANK, OPG, IL-8, IL-6, and the OPG/sRANKL ratio were significantly higher, while the level of MMP-2 was significantly lower in patients with bone tumors than in controls. Serum concentration of IL-16 in osteosarcoma patients was significantly lower than in chondrosarcoma patients. No significant differences between bone sarcomas of different differentiation were detected for any of the studied markers. Calcitonin level depended on the tumor location and type.

Biochemical markers of brain tumours.

The paper presents the results of neurospecific proteins S-100 and glial fibrillary acidic protein (GFAP) determination in blood serum samples of 145 neuro-oncology patients and 69 healthy people. The significant elevation of S-100 and GFAP was revealed in glioblastoma (G IV) patients compare to the patients with anaplastic astrocytoma (G III), benign meningioma (GI), celebral metastasis and healthy controls. The concentration of S-100 in blood serum of patients with anaplastic astrocytoma, benign meningioma, and celebral metastasis did not significantly differ among themselves, and in relation to the control group there was a significantly increase only in patients with cerebral metastasis. GFAP was characterized by high frequency of its detection in patients with glioblastoma (83%) compare to other groups of patients and healthy donors, in which it was practically undetectable. These data suggest the possibility of using GFAP as a marker of glioblastoma and S-100- as an additional biochemical criteria of cerebral lesions in oncology patients.

Granulosa cell tumors of the ovary and inhibin B.

We present the results of immunoenzyme detection of inhibin B in blood serum of patients with adult-type granulosa cell tumors of the ovary. Blood concentration of inhibin B at the end of menstrual cycle in patients with tumor relapse was significantly higher than in patients during remission and in virtually healthy women. The increase in inhibin B concentration preceded clinical manifestation of the disease relapse by 2-13 months, which demonstrates high diagnostic sensitivity of this marker and suggests that it can be recommended for the use in diagnostics and monitoring of granulosa cell tumors of the ovaries.

Neurospecific proteins in the serum of patients with brain tumors.

Neurospecific proteins S-100 and GFAP were measured in the serum of 145 patients with neural tumors and 69 healthy individuals. In patients with glyoblastomas, the concentrations of S-100 and GFAP were significantly higher than in patients with anaplastic astrocytomas, benign meningiomas, and brain metastases and in healthy individuals. Serum S-100 concentrations in patients with anaplastic astrocytomas, benign meningiomas, and brain metastases were similar; significant difference from the control was found only for patients with cerebral metastases. A specific feature of GFAP was high incidence of its detection in patients with glioblastomas (83%) compared to other groups of patients with neural tumors and healthy volunteers who demonstrated practically zero level of this protein. These findings attest to the possibility of using S-100 as an additional biochemical criterion of brain involvement in tumor patients and GFAP as a glioblastoma marker.

Serum angiogenic factors in patients with neuroendocrine tumors of abdominal organs.

The initial (before treatment) levels of VEGF, endostatin, and tumor necrosis factor-beta (TNF-beta) were measured in the sera of 20 patients with malignant and benign neuroendocrine tumors of the abdominal organs and 25 healthy controls. The initial levels of VEGF, endostatin, and TNF-beta in the total group of patients with neuroendocrine tumors of abdominal organs did not differ from the control. A significant difference was detected between the mean serum concentrations of endostatin in patients with benign and malignant neuroendocrine tumors: 64.1+/-14.7 and 107.8+/-14.1 ng/ml, respectively (p=0.043). The content of VEGF, endostatin, and TNF-beta did not correlate with patients' gender and age. A direct correlation between endostatin, TNF-beta concentrations and maximum size of the primary tumor was detected in patients with malignant neuroendocrine tumors. Direct correlations between the initial levels of VEGF and endostatin and an inverse correlation between VEGF and TNF-beta concentrations were detected in patients with benign neuroendocrine tumors. Relapse-free survival was significantly lower in patients with serum endostatin concentration >100 ng/ml and TNF-beta<30 pg/ml.

In vivo radioprotection of mouse brain endothelial cells by Hoechst 33342.

Radiation-induced loss of mouse brain endothelial cells has been examined in mice given an intravenous injection of the DNA-binding radioprotector Hoechst 33342 (80 mg kg-1). At the time of irradiation, 10 min after injection, Hoechst fluorescence in the brain was confined to the endothelial cells. Endothelial cell density was measured using a histochemical fluorescence technique that had been used previously to monitor post-irradiation changes in endothelial cell density in rat brain, in which it was shown that a sensitive subpopulation comprising about 15% of the endothelial cells was lost within 24 h of radiation exposure. The present study shows a similar dose-response for the control mice, with depletion of the sensitive subpopulation to 85% being almost complete after a dose of 2.5 Gy gamma-rays. However, in mice irradiated 10 min after Hoechst 33342 administration, doses between 12 Gy and 20 Gy were required to ablate these cells. The kinetics of cell loss and the rather large dose modification factor suggests that Hoechst 33342 may be suppressing an apoptotic response in this subpopulation. Whatever the mechanism involved, Hoechst 33342 clearly provides substantial protection against early radiation-induced endothelial cell loss. Further studies are necessary to determine the extent to which this initial protection translates into an improved long-term survival of the "protected" cells and, especially, to see whether this endothelial cell protection can ameliorate the later consequences of central nervous system irradiation, namely necrosis and paralysis.

Laccase from Coriolus hirsutus as alternate label for enzyme immunoassay. Determination of pesticide 2,4-dichlorophenoxyacetic acid.

A new label--laccase from the fungus Coriolus hirsutus--was applied for solid-phase enzyme-linked immunosorbent assays of the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D). Two proposed assays are based on (1) competitive binding of antibody-laccase conjugate with immobilized 2,4-D-protein conjugate and 2,4-D in tested sample, and (2) competition of 2,4-D and 2,4-D-laccase conjugate for binding with immobilized antibodies. Kinetic and concentration dependencies for these reactions were studied, and the ELISAs were optimized in accordance with the data obtained. The elaborated systems permit the detection of 2,4-D in concentrations down to 10-20 ng/mL; time of the assays is 1.5-2 h. The main advantage of the laccase label, in comparison with the widely used peroxidase one, lies in the lack of hydrogen peroxide from substrate mixture, because dissolved oxygen plays the role of oxidizer.

Analysis of elastase 1 for evaluation of excretory function of the pancreas after gastropancreatoduodenal resection.

The level of elastase 1 in feces was markedly decreased in all patients with tumors of the pancreatic head or its involvement before and after gastropancreatoduodenal resection and was close to normal in patients with retroperitoneal tumors not invading the pancreas. Serum elastase 1 concentrations were virtually the same in patients, normal subjects, and patients without signs of pancreatic involvement. The presence of elastase 1 in feces reflects adequate function of the pancreato-digestive anastomosis, while low concentrations of the enzyme indicate impaired function of the pancreas, presumably because of operation trauma and tumor process. Measurement of elastase 1 in feces is a highly informative and specific test for evaluation of pancreatic function in patients with pancreatic tumors, which can be used in clinical practice.

Impaired production of plasma interleukin-6 in patients with Parkinson's disease.

The contents of interleukin-6 in the plasma from patients with Parkinson's disease and endogenous depression were compared by enzyme immunoassay. Interleukin-6 content in the plasma increased in the early stage of idiopathic parkinsonism complicated by depressive syndrome. A correlation was found between interleukin-6 content and changes in higher mental activity estimated by neuropsychological tests.