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Biomedical subjects

N E Kushlinskiĭ

Publications and source records attributed to N E Kushlinskiĭ.

At least 19 recordsLinked to original sources

[Diagnostic significance of type IV collagen and hyaluronic acid in the serum of patients with chronic hepatitis C for staging hepatic fibrosis].

AIM: To evaluate diagnostic value of serologic fibrosis markers (hyaluronic acid--HA and type IV collagen C-IV) in patients with chronic hepatitis C (CHC) and hepatic cirrhosis (HC). MATERIAL AND METHODS: HA and C-IV were measured in 88 CHC patients with fibrosis stage 1 (n = 63) and 3 (n = 25), 13 patients with acute hepatitis C (AHC), 28 patients with hepatic cirrhosis (HC), 19 patients with pulmonary fibrosis (PF). The control group consisted of 32 healthy subjects. RESULTS: HA concentrations in the serum of CHC patients with mild to severe inflammation and fibrosis (F1 and F3) were normal (100 ng/ml). For HC diagnosis, HA test proved highly sensitive and specific (in HA 100 ng/ml sensitivity was 100%, specificity 84.6%), but this method cannot stage hepatic fibrosis. HA test was inferior to C-IV test. A mean C-IV concentration in the serum of CHC patients at the stage of marked fibrosis (F3) is significantly higher than in F1, in HC (A) patients higher than in patients with CHC F3. CONCLUSION: It is shown than concentration of C-IV above 196 ng/ml can differentiate fibrosis stage 1 from stage 3 with specificity 58.7 and sensitivity 88%.

Adult↗

[Vascular endothelial growth factor in patients with prostate cancer and benign prostatic hyperplasia].

The authors examined 25 patients with prostate cancer (PC) and 36 patients with benign prostatic hyperplasia (BPH). In the group of patients with morphologically verified PC mean serum level of vascular endothelial growth factor (VEGF) was significantly higher than in patients with BPH (p < 0.05). The study demonstrated strong negative association between VEGF and prostate specific antigen (PSA) levels (r = 0.72, p < 0.05) in PC patients. There was no association between VEGF serum level and the stage or malignancy of PC (Gleason score). In benign prostatic glands moderate VEGF expression was observed only in basal cells, whereas in cases of PC all tumor cells displayed active VEGF expression; the difference was significant (p < 0.05). High serum VEGF levels and its active expression in patients with PC suggest an important role of angiogenic factors in the pathogenesis of this disease. The negative association between VEGF and PSA serum levels in PC indirectly confirms antiangiogenic activity of PSA, shown before.

Aged↗

[Vascular endothelial growth factor and two types of its receptors in breast cancer].

Levels of VEGF, VEGFR-1 and VEGFR-2 were determined by enzyme immunoassay in tumor and adjacent normal tissue samples from 39 breast cancer patients. Those parameters were significantly higher in tumor tissue. Direct correlations were established between VEGF and VEGFR-1, on the one hand, and VEGF and VEGFR-2, on the other. VEGF expression in breast tumor was relatively higher at earlier stages of tumor growth. VEGF and VEGFR-1 expression was consistently higher in progesterone receptor negative tumors.

Adult↗

[The features of expression of cellular adhesion molecules in primary colorectal cancer and its metastases].

Features of expression, distribution and interaction of E-cadherin, beta-catenin and CD-44v6 were immunologically assayed in samples from primary colorectal tumors (129) and their metastases to the lymph nodes (35) and liver (92). Reduction or total absence of E-cadherin expression was significantly more typical of tumors metastasizing, at different stages, to the liver (64/84, 76%) than in metastasis-free ones (14/45, 31%) (p=0.014). Enhanced cytoplasmic immunoreactivity and beta-catenin nuclear translocation occurred in 80% of disseminated tumors. Such alterations of E-cadherin, beta-catenin expression may be regarded as unfavorable prognosis factors involved in colorectal cancer. No significant correlation between CD-44v6 expression and tumor cell ability to metastasize was recorded.

Adult↗

[The specificity of expression of molecular biological markers in tumors of the mammary gland].

Data are described on a retrospective immunohistochemical study of the Ki-67, PCNA, Bcl-2, BAX, BclX and VEGF expression in tumors of two groups of patients with breast cancer (BC) and with the favorable and unfavorable clinical courses. A reliably high level of VEGF expression was detected in tumors of patients with an early BC relapse. Apart from VEGF, higher levels of the Ki-67 and PCNA expression were registered in tumors of the discussed patient's category. It can be suggested that the expression parameters of VEGF, Ki-67 and PCNA in the primary tumor can be made use of in evaluating the BD prognostications or describing the features of high-risk groups with a high probability of early disease relapses.

Adult↗

[Urokinase and tissue type plasminogen activators and their type-1 inhibitor (PAI-1) in gastric cancer].

The levels of urokinase (uPA) and tissue type (tPA) plasminogen activators and their type 1 inhibitor (PAI-1) were determined by immunoassay in tumor cytosols and samples of histologically unaltered adjacent mucosa in gastric cancer patients. Gastric tumor revealed enhanced uPA and PAI-1 matched by decreased tPA in intact mucosa. The expression of uPA and PAI-1 was particularly was high at the later stages of the disease. The concentrations of uPA in tumor tissue increased with age. No significant correlation was established between levels of plasminogen activation system components, on the one hand, and histopathological grading of tumor, on the other.

Adolescent↗

[Vascular endothelial growth factor and plasminogen activators in endometrial carcinoma and hyperplasia].

Vascular endothelial growth factor (VEGF) and such plasminogen activation system components as uPA, PAI-1 and tPA were determined by enzyme immunoassay methods in endometrial tumors from 121 patients and 18 samples of endometrial hyperplasia of varying degree. Endometrial carcinoma concentrations of uPA vs. PAI-1 were significantly higher than those in hyperplasia. Significant direct correlations--uPA vs. VEGF, uPA vs. PAI-1 and PAI-1 vs. VEGF--were established in endometrial tumors, and inverse ones for tPA vs. uPA and tPA vs. VEGF. A marked correlation with prognostic factors was found for PAI-1 and VEGF: levels of these proteins were relatively higher in cases of tumor progression (FIGO stage and deeper myometrial invasion), poor cell differentiation, and loss of hormone sensitivity. Higher uPA expression was associated with deeper myometrial invasion while, in endometrial tumors with unfavorable prognosis, it was VEGF level alone that was significantly higher.

Adult↗

[Growth receptor factor and steroid hormones: their diagnostic value in differential diagnosis of neoplasms in children].

The distribution of epidermal growth factor receptors (EGFR) and receptors for steroid hormones--androgens (RA), estrogens (RE) and glucocorticoids (RG) was studied in malignant (MT) and benign (BT) tumors in children. The distribution and mean levels of some receptors in normal tissues were statistically different from those in MT and BT. The absence of RA and the high levels of RE > 20 fmol/mg protein and RG > 50 fmol/mg protein were typical of MT whereas BT might be characterized by the high levels of EGFR > 300 fmol/mg protein. In MT with and without metastases, the following parameters were significantly different (p < 0.001): RG = 81 and 18 fmol/mg, respectively, and EGFR = 160 and 58 fmol/mg protein, respectively. The most informative parameters for distinguishing BT and MT appeared to be RA (0.086 dit), RE (0.043 dit) and EGFR (0.037 dit). The most sensitive parameter for MT was RG, which, however, is least specific; RA is most specific (75%). The optimal amount of three parameters: RA + RE + EGFR (88.4%) is most exact for differential diagnosis.

Adolescent↗

[Osteosarcoma: biochemical and endocrinological studies as a basis for its pathogenetic treatments].

The paper considers data of the long-term studies of androgen metabolism, baseline serum levels of reproductive steroid hormones and their receptors in the tumor, in the blood concentrations of sex steroid-binding globulin and pituitary hormones, the expression of epidermal growth factor, its receptors and ligands, soluble Fas-antigen, vascular endothelial growth factor, angiogenin, and the content of calmodulin, cAMP in the osteosarcoma in 300 patients aged 14 to 56 years, which were made at the N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences. Analyzing the findings identified some lines in the study of new pathogenetic treatments for osteosarcoma, aimed at regulating androgen metabolism, correcting the cyclooxygenase pathway of arachidonic acid, the expression of receptors of epidermal growth factor and its ligands, the processes of neoangiogenesis in the tumor. A role of the above parameters in the pathogenesis of osteosarcoma is discussed.

Bone Neoplasms↗

[Expression of the apoptosis inhibitor soluble Fas antigen in patients with malignant and benign bone neoplasms].

This paper presents results of comparative enzyme immunoassay of soluble serum Fas antigen (sFas) in 98 patients with benign and malignant bone tumors, 15 patients with mechanical bone traumas, and 60 normal individuals of compatible age. The prevalence and concentration of sFas were significantly greater in patients with bone tumors than in normal donors and patients with mechanical bone traumas. The association of sFas with the pathogenesis of primary bone tumors is discussed in the paper.

Adolescent↗

[Hormones, autocrine and paracrine regulators of tumor growth in osteosarcoma].

The data on 300 patients, aged 14-56, treated at the Center's Clinic have been evaluated. They include findings on androgen metabolism, basal level of secretion of sex steroid hormones in blood serum and their receptors in tumor, blood concentrations of sex steroids, binding globulin and pituitary hormones, arachidonic acid metabolism, expression of epidermal growth factor and its receptors and ligands, soluble Fas-antigen, vascular endothelial growth factor as well as calmodulin and cAMP levels in sarcoma. New trends of research in pathogenetic methods of treatment of osteosarcomas used in practice of oncology have been identified. Among them are androgen metabolism regulation, correction of the cyclooxygenase pathway of arachidonic acid metabolism, expression of epidermal growth factor and its ligands and neoangiogenesis in tumor.

Adolescent↗

[Plasminogen activators of urokinase and tissue types and their inhibitor (PAI-1) in cytosol fraction in thyroid diseases].

Enzyme immunoassay (ELISA) was used to estimate the levels of plasminogen activators of urokinase (uPA) and tissue (tPA) types and one of their inhibitors (PAI-I) in the cytosolic fraction of the thyroid in 129 patients with malignant and benign tumors and various non-cancer diseases of the gland. Tumors from patients with thyroid cancer displayed the lowest levels of tPA and the highest levels of uPA and PAI-I, while those from patients with benign thyroid diseases, including adenoma, had high concentrations of tPA and relatively low levels of uPA and PAI-I in the tissue of the diseased organ. At the same time, the lowest levels of uPA and PAI-I were found in patients suffering from toxic goiter with and without adenomatosis. In terms of uPA and PAI-I levels, patients with nodular colloidal goiter were intermediate between those with toxic goiter and adenoma, on the one hand, and those with thyroid cancer, on the other.

Adenoma↗

[Treatment of limb osteosarcoma at the turn of the century (half century of experience in research)].

The Russian Cancer Research Center has experience in diagnosing and treating more than 800 patients with osteosarcoma who have been treated at the Clinic of General Oncology since 1952. Survival rates were no more than 10% before the 1970s when the only treatment was surgical. The use of adjuvant chemotherapy after radical surgery has increased survival up to 45-60%. In 1982 to 1986, a protocol involving intraarterial chemotherapy with adriamycin, 90 mg/m2, radiation therapy in a dose of 40 Gy, preserving surgery, and adjuvant chemotherapy was used to improve local and regional guidance. Survival was 55-60%. The high incidence of purulent complications prompted us to do away with radiation therapy. A protocol of neoadjuvant therapy that implies preoperative intraarterial monotherapy with cisplatin, 120-150 mg/m2, adriamycin, 90 mg/m2 or large-dose methotrexate (8-10 g/m2) was implemented in 1986 to 1998. The best results were achieved only in patients with complete tumor necrosis, among whom survival being over 70%. Preserving surgery following ineffective chemotherapy caused a high incidence of local relapses (30%). The second line of chemotherapy did not greatly improve prognosis when a histological response was slight. Complete tumor necrosis was noted only 10% of more than 150 patients so survival in the whole group was 40%. In 1998, a new protocol was initiated to improve immediate and late outcomes. Preoperatively, 3-4 sessions with adriamycin, 90 mg/m2 and cisplatin, 120 mg/m2, are performed. Postoperatively, 3 or 4 sessions of chemotherapy with the same drugs are made if there is a marked therapeutical pathomorphism. If a response is weak, 6 sessions with ethoposide, 100 mg/m2 and iphosphamide, 1.8 g/m2 during 1-5 days are given. This study has covered just 30 patients. The rate of a full histological responses has increased by 4 times. In every second patient, an amputable tumor could be made a resectable one. The proportion of candidates for preserving surgery has increased up to 90%. Intensified chemotherapy increased the incidence of severe adverse effects, primarily degrees 3-4 hematological toxicity reaching 40%. At the turn of centuries, osteosarcoma is a highly promising curable disease. The survivals of 65-70% and satisfactory functional results can be achieved only at highly specialized centers.

Bone Neoplasms↗

[Modern prospects for molecular-biochemical methods for evaluating biological "behavior" of breast neoplasms].

The paper presents recent data on the role of oncogenes and suppressive genes, receptors of steroidal hormones, secretory protein pS2, cathepsin D, urokinase and tissue plasminogen activators and their inhibitor PAI-I, polypeptide growth factors and somatostatin and their receptors in the evaluation of proliferative activity and drug therapy responses and in the prediction of disease and on the simultaneous estimation of the limited number of mutually complementing parameters that can characterize the proliferative activity of a tumor, its metastatic potential and sensitivity to different types of overall and regional regulation. The main task for investigators engaged in this area is to choose a qualitatively and quantitatively optimal ratio of molecular markers of breast cancer to evaluate the biological behavior of a tumor.

Breast Neoplasms↗

[The pharmacological and hormonal effects of carbamazepine and valproic acid in the treatment of reproductive age women with epilepsy].

Dynamics of steroid hormone (extradiol-17 beta, progesterone, total testosterone and cortisol) concentrations in the middle of follicular and lutein menstrual cycle phases has been studied in women with epilepsy aged 21-30 years. Nineteen patients were treated with valproic acid (depakine--900-2000 mg/day), 35--with carbamazepine (500-1200 mg/day). All the patients have been treated during at least 6 months, paroxysms being not registered during the last 3 months before blood analysis. Control group consisted of 17 healthy age-matched women with no positive familial history of nervous and endocrine diseases. Comparing to the control, the affected groups revealed a significantly lower estradiol level (p < 0.003) during the follicular phase and higher cortisol concentrations during both the follicular and the lutein phases (p < 0.05). Regardless of menstrual cycle phases, the differences in progesterone and total testosterone concentrations have not been found between subgroups treated by carbamazepine and depakine. The same hormonal deviations detected after using both carbamazepine and Depakine in the homogenous subgroups of the patients imply, to a certain extent, a common character of pathogenetic mechanisms for steroid hormone pattern development in women with epilepsy. Carbamazepine and depakine treatment during at least 6 months does not predispose to ovary polycystosis syndrome. The results support a multifactor character of hormonal deviations in epilepsy and do not show the medication factor as a major one.

Adult↗