ABSTRACT
The study included 44 patients with Stage Ia1 - lb1 cervi- cal cancer who underwent organ-preserving surgery (transab- dominal trachelectomy). To visualize sentinel lymph nodes - lymphoscintigraphy with injection of radioactive lymphotropic isotope - (99m)Tc-labelled nanocolloid was injected a day before surgery. Intraoperative identification of sentinel lymph nodes using gamma probe was carried out to assess, which lymph nodes had taken up the radionuclide. Detection of sentinel lymph nodes in cervical cancer patients could accurately predict the pelvic lymph node status, assess the stage of the dis- ease, individualize the extent of surgery and determine indica- tions for organ-preserving surgery.
Subject(s)
Lymphoscintigraphy , Sentinel Lymph Node/diagnostic imaging , Trachelectomy , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/surgery , Adult , Female , HumansABSTRACT
The aim of the study was to investigate the serum adipokine levels and expression of adipokine receptors (AdipoR1, AdipoR2) in patients with endometrial and colon cancer in relation with the main clinical morphological parameters (tumor invasion, lymph node involvement). The study included 60 endometrial cancer patients with I-II Stage and 31 patients with colon cancer (T2-4N0-2M0). Serum adipokine levels, the level of soluble form of the leptin receptor (sOb-R) and AdipoR1 and AdipoR2 expression were evaluated with ELISA. In endometrial cancer serum leptin and adiponectin levels were associated not only with metabolic disorders but also with cervical invasion. In colon cancer serum leptin level was associated with lymph node involvement. The data obtained showed the potential implication of serum adipokines into tumor invasion and metastasis. In both sites intratumoral levels of AdipoR1 H AdipoR2 were not associated with the presence of metabolic syndrome. The AdipoR1 level was related with myometrial invasion. In colon cancer patients, AdipoR1 and AdipoR2 expressions were associated with lymph node involvement, and AdipoR1 expression was correlated with tumor size. The obtained results demonstrated involvement of adipose tissue hormones (leptin and adiponectin) and adiponectin receptors (AdipoR1 and AdipoR2) in tumor growth, invasion and lymphogenic metastasis.
Subject(s)
Adipokines/blood , Cervix Uteri/pathology , Colonic Neoplasms/pathology , Endometrial Neoplasms/pathology , Receptors, Adiponectin/analysis , Adiponectin/blood , Adult , Aged , Colonic Neoplasms/blood , Colonic Neoplasms/chemistry , Endometrial Neoplasms/blood , Endometrial Neoplasms/chemistry , Enzyme-Linked Immunosorbent Assay , Female , Gene Expression Regulation, Neoplastic , Humans , Leptin/blood , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness , Neoplasm StagingABSTRACT
Activity of the proteasome, polyfunctional enzymatic complex, is known to undergo changes during cancer development. This phenomenon is, probably, caused by the changes in subunit composition of proteasomes. In present work, we studied chymotrypsin-like activity of proteasomes, subunit composition and their association in breast cancer, head and neck squamous cell carcinoma, endometrial cancer, renal cancer, bladder cancer, stomach cancer and colorectal cancer. The increase of proteasome activity was revealed in most cancer tissues compared with adjacent tissues except for the renal cell carcinoma. Changes in proteasome activity in cancer tissues compared with correspondent normal tissues were accompanied by modification of its subunit composition. High proteasome activity was observed in combination with an increased expression of immune subunits and/or proteasome activator PA28, associated with activity of 20S proteasome. In breast cancer, head and neck squamous cell carcinoma, bladder cancer, stomach cancer and colorectal cancer we additionally found higher expression of Rpt6 subunit of 26S proteasome. Correlations between chymotrypsin like proteasome activity and subunit expressions were found in human cancer tissues. In summary, we suggest that proteasome ac- tivation and changes in its subunit composition plays an important role in cancer pathogenesis.
Subject(s)
Chymases/metabolism , Neoplasms/enzymology , Proteasome Endopeptidase Complex/metabolism , ATPases Associated with Diverse Cellular Activities , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Cell Line, Tumor , Humans , LIM Domain Proteins/genetics , LIM Domain Proteins/metabolism , Muscle Proteins/genetics , Muscle Proteins/metabolism , Proteasome Endopeptidase Complex/genetics , Protein Subunits/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
We have examined for the first time the relationship between the expression of PAPP-A metalloproteinase and insulin-like growth factors (IGF-I, IGF-II, VEGF) and transcription factors (NF-kappaB, HIF-1) playing an important role in pathogenesis of cancer. We also demonstrated a positive association between the level of PAPP-A metalloproteinase and the level of growth (VEGF and IGF-I) and transcription factors (NF-kappaB p50, NF-kappaB p65, HIF-1alpha). The current findings suggest an important role of PAPP-A in regulation of bioavailability of IGF-I, VEGF, activated forms of NF-kappaB, and alpha-subunits of HIF-1 in endometrial tumors.
Subject(s)
Endometrial Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Pregnancy-Associated Plasma Protein-A/metabolism , Endometrial Neoplasms/pathology , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor II/genetics , Insulin-Like Growth Factor II/metabolism , Middle Aged , NF-kappa B/genetics , NF-kappa B/metabolism , Neoplasm Staging , Pregnancy-Associated Plasma Protein-A/genetics , Transcription Factors/biosynthesis , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
We conducted a comparative investigation of the hormonal status (LH, FSH, estradiol, progesterone, testosterone, prolactin, SHBG), energy status (leptin, ghrelin, insulin), and carbohydrate and lipid metabolism in patients with endometrial hyperplasia and neoplasia (168 patients) with or without metabolic syndrome in the background. Patients with metabolic syndrome had a high frequency of elevated estrogen (72%), testosterone (65%), insulin (81%), leptin (68%). There was a marked increase in the basal level of luteinizing hormone, prolactin, index, LH/FSH, but decrease in FSH and progesterone. There were significant changes in carbohydrate and lipid metabolism. The possible mechanisms for the contribution of the investigated factors to the development of the pathological processes in the endometrium are presented.
Subject(s)
Dietary Carbohydrates/metabolism , Endometrial Hyperplasia/blood , Endometrial Hyperplasia/complications , Endometrial Neoplasms/blood , Endometrial Neoplasms/complications , Gonadal Steroid Hormones/blood , Lipid Metabolism , Metabolic Syndrome/blood , Metabolic Syndrome/complications , Adult , Aged , Endometrial Hyperplasia/metabolism , Endometrial Neoplasms/metabolism , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Ghrelin/blood , Humans , Insulin/blood , Leptin/blood , Luteinizing Hormone/blood , Metabolic Syndrome/metabolism , Middle Aged , Progesterone/blood , Prolactin/blood , Sex Hormone-Binding Globulin/metabolism , Testosterone/bloodABSTRACT
The development of endometrial cancer is related to the status of the intracellular proteasome system. Total proteasome activity and pools 26S and 20S activities are higher in tumor tissue than in intact endometrium, and their composition is different. The expression of α1α2α3α5α6α7 is lower in endometrial cancer tissue in comparison with intact endometrium and the content of immune subunits LMP7, LMP2, and PA28ß is increased. Total proteasome activity depends on the disease stage.
Subject(s)
Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Endometrium/metabolism , Proteasome Endopeptidase Complex/metabolism , Protein Subunits/metabolism , Electrophoresis , Female , Humans , Middle Aged , Statistics, NonparametricABSTRACT
A mathematical model based on principles of multifactor analysis was developed to predict clinical outcome of endometrial hyperplasia (EH) in patients with metabolic syndrome (80). Seventy-seven factors--anthropometric, clinical, anamnestic, hormono-metabolic, immunohistochemical, etc.--were included. Evaluation of the most informative indices integrated with the discriminative model showed that anthropometric (waist and hip circumference, sagittal diameter, etc.) and clinico-anamnestic (age, age of secondary sexual characters appearance, body weight at birth, suckling pattern, etc.) ones are of similar significance. A profile of hormono-metabolic parameters (cholesterol-low density lipoprotein, leptin, testosterone, progesterone and fasting glucose levels) helped identify a wide range of EH-related disorders in patients with metabolic syndrome. Consistently with the literature data, level of PTEN expression pointed to the presence of this tumor's suppressor in most EH cases which was matched by absence of its expression in endometrial carcinoma. Our model provided high sensitivity (89%) and specificity (82%) in predicting risk of progression in patients with endometrial hyperplasia and metabolic syndrome.
