Receptor Activator of Nuclear Transcription Factor NF-κB (RANK), Its Ligand RANKL, and Natural Inhibitor of RANKL Osteoprotegerin (OPG) in the Blood Serum of Patients with Primary Bone Tumors.

The content of components of the RANK/RANKL/OPG system, the key regulator of homeostasis in the bone tissue, in blood serum samples from 199 patients with primary bone neoplasms and 131 practically healthy volunteers was measured by ELISA. Borderline giantcell tumor of the bone with high osteoclastogenic and osteolytic activity is characterized by an increase in the level of all components of this system and highest ratio of sRANKL/OPG in the blood serum. Study indexes in patients with various benign neoplasms and tumor-like bone lesions were lower than in patients with giant-cell tumor. The patients with malignant bone tumors could be divided into 2 subgroups with opposite indexes of the RANK/RANKL/OPG system. The patients with osteosarcoma and Ewing sarcoma had a low level of sRANK, but a high level of sRANKL. The patients with chondrosarcoma and chordoma had a high level of sRANK, but a low level of sRANKL.

Insulin-like growth factors (IGF), IGF-binding proteins (IGFBP), and vascular endothelial growth factor (VEGF) in blood serum of patients with colorectal cancer.

Serum levels of insulin-like growth factors (IGF-1 and IGF-2), IGF-binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3) and vascular endothelial growth factor (VEGF) were measured by standard ELISA technique in 95 primary colorectal cancer patients and 48 healthy individuals. Significant increase in serum levels of IGF-1, IGFBP-2, and VEGF and decrease in IGFBP-3 level were demonstrated in patients in comparison with the control group; in male patients, serum level of IGF-2 was also increased. Sensitivity of IGF-1 as the prospective diagnostic marker of colorectal cancer was 80% and specificity was 75% at the threshold level of 140 ng/ml. Serum levels of IGF-1 significantly decreased with age in both patients and healthy donors, but in patients, this correlation was much weaker. These parameters did not correlate with the main clinical and morphological indices, such as dissemination, localization, and histological structure of colorectal cancer.

Content of matrix metalloproteinase-8 and matrix metalloproteinase-9 in oral fluid of patients with chronic generalized periodontitis.

The content of MMP-8 and MMP-9 in oral fluid of 145 patients (95 women and 50 men, 18-52 years) was measured by enzyme immunoassay. We examined 63 subjects with the intact periodontium and 82 patients with chronic generalized periodontitis (25 patients with mild disease, 45 patients with moderate disease, and 12 patients with severe disease). All patients were examined during the remission of chronic periodontitis and did not have clinical signs of associated somatic diseases. No significant differences were found in the content of MMP-8 and MMP-9 in oral fluid from periodontitis patients and subjects with the intact periodontium. The content of MMP-8 an MMP-9 in oral fluid of patients with severe periodontium was slightly higher than that in other patients and subjects with the intact periodontium. The depth of the periodontal pocket was shown to be the most reliable clinical sign for the state of periodontal tissues. A strong correlation was revealed between this criterion and MMP-9 content in oral fluid.

[Epidermal growth factor receptors in malignant and benign tumors in children]. / Retseptory épidermal'nogo faktora rosta v zlokachestvennykh i dobrokachestvennykh opukholiakh u detei.

The radioligand technique was used to study the amount of epidermal growth factor receptors (EGFR) in malignant and benign tumors in 32 children aged 8 months to 17 years. The membranous fraction of 11 of the 32 tumors studied showed EGFR equal to 10.1 to 1327 fmol/mg (163.0 +/- 117.5 fmol/mg, median 38.0 fmol/mg). The greatest amount of EGFR was found in breast fibroadenomas. There was no clear relationship of the frequency and level of EGFR expression to a nosological tumor entity in children. A possible role of the EGFR system in tumors in children is discussed.

[EFR-like peptides and their receptors as prognostic factors for the survival of patients with non-small-cell lung cancer]. / Sistema EFR-podobnykh peptidov i ikh retseptorov kak faktor prognoza vyzhivaemosti bol'nykh nemelkokletochnym rakom lëgkogo.

The levels of EGFR and its ligands have been assayed in tumor and adjacent lung tissues in NSCLC patients. Both EGFR and EGF-like peptides were found in tumor more frequently than in unaltered tissue. It was shown (Kaplan-Meyer) that simultaneous expression of EGFR and its ligands in tumor and adjacent lung tissues was associated with lower overall and relapse-free survival in NSCLC patients.

[Epidermal growth factor receptors and their ligands in non-small-cell lung carcinoma]. / Retseptory épidermal'nogo faktora rosta i ikh ligandy pri nemelkokletochnom rake legkogo.

Investigators and clinicians have recently called attention not only to the clinical and morphological parameters, but to the parameters characterizing the biological activity of nonsmall-cell carcinoma of the lung (NSCCL) from biochemical and molecular biological points of view. These include production of epidermal growth factor (EGF) receptors (EGFR) and their ligands which are important auto/paracrine regulation of lung tissue formation in health and tumor growth. Active studies of EGFR and EGF-like peptides (mainly, EGF and alpha-TGF) have failed to gain an insight into their role in the pathogenesis of NSCCL. Most authors suppose that tumor EGFR production increases as cell atypical features enhance and tumors show EGFR hyperexpression as compared with intact lung tissue. The expression of EGF and alpha-TGF is associated with poor prognosis in NSCCL. Attempts at designing and clinically testing the agents that block the transmission of EGFR ligands within the tumor cell are well-known, which open up new possibilities for antitumor therapy of patients with NSCCL.

Comparative analysis of the sensitivity of endometrial cancer cells to epidermal growth factor and steroid hormones.

BACKGROUND: Epidermal growth factor (EGF) and EGF-regulated processes play an important role in steroid signal transduction. Comparative analysis of EGF and steroid receptor expression and the sensitivity of early stages of proliferation induction, such as activation of phospholipid turnover to EGF and steroids, may provide a useful new approach to characterizing the sensitivity of endometrial cancer to hormone therapy. METHODS: Progesterone (PR), estradiol (ER), and EGF receptor (EGFR) content was measured by radioligand competitive methods in surgically excised tumors from 26 patients with primary endometrial cancer. In short term cell cultures isolated from 11 of these tumors, the influence of a 10-minute treatment with 10(-8)M EGF either alone or combined with 10(-8)M progesterone on 32P-incorporation into phospholipids was studied. Phospholipids were fractionated by thin-layer chromatography and were located by autoradiography, and quantification of the labeled compounds was made by densitometric scanning of the autoradiograms. RESULTS: Epidermal growth factor receptor was found in 15 of 26 (58%) endometrial cancer samples. Eighty-two percent of the tumors studied contained PR, and 81% contained ER. No significant correlations were revealed between EGFR and ER/PR status or concentration. Epidermal growth factor stimulated 32P-incorporation by more than 120% of the control level in five of seven EGFR-positive and in one of four EGFR-negative endometrial cancer samples. An inverse relationship was revealed between EGFR content and the percentage of EGF-induced stimulation of phospholipid turnover in endometrial cancer cells (r = -0.6; P = 0.15) and between EGFR content in EGFR-positive samples and the extent of progesterone suppression of EGF-induced turnover (r = -0.77; P = 0.04). CONCLUSIONS: Determination of EGF sensitivity on a receptor and a functional level may provide important additional information about the hormonal sensitivity of endometrial cancer.

[Interaction of tamoxifen with cytosol estradiol receptors in myoma and histologically unchanged myometrium]. / Vzaimodeistvie tamoksifena s tsitozol'nymi retseptorami éstradiola miomy i gistologicheski neizmenennogo miometriia.

The relative binding affinity of nonsteroidal antiestrogen tamoxifen to the cytosol estradiol receptors of hyperplastic and unaltered myometria in patients with leiomyoma has been studied. Relative binding affinity of tamoxifen in tumor tissues exceeded one in normal myometrium.

[The pathogenetic basis for using antiestrogens in treating patients with hyperplastic processes of the endometrium in the postmenopause]. / Patogeneticheskoe obosnovanie primeneniia antiéstrogenov v lechenii bol'nykh s giperplasticheskimi protsessami éndometriia v periode postmenopauzy.

Estradiol and progesterone cytosol receptors, tamoxifen relative binding capacity in endometrial tissue samples, serum estradiol and progesterone levels were studied in 60 postmenopausal patients with hyperplastic processes in the endometrium. Estradiol and progesterone receptor levels were increased in glandular cystic polyp tissue, in atypical hyperplastic tissue samples, and in well-differentiated adenocarcinoma tissue. High estradiol levels were detected in the blood sera of patients with glandular cystic polyps, atypical and glandular hyperplasia. Tamoxifen relative binding capacity was the highest in glandular cystic polyps and glandular hyperplasia. Forty patients were treated with 17-hydroxyprogesterone capronate. The data on the status of cytosol receptors and tamoxifen relative binding capacity as well as clinical findings give grounds to include antiestrogens into therapeutic complex for postmenopausal patients with endometrial hyperplasia.