thymosin and Adenoma

Despite major advances in its diagnosis and treatment, gastric cancer (GC) remains a major life-threatening disease. Treatment of the disease is further aggravated by the lack of diagnostic biomarkers that can aid in the early detection of GC and promote its favorable prognosis. The present work aims to identify novel diagnostic biomarkers for GC.. The present work is a case-control study that focuses on proteomic analysis of serum from healthy volunteers and GC patients using ClinProt profiling technology based on mass spectrometry. A pattern of proteins/peptides with the ability to differentiate the studied populations was identified. Deregulated proteins/peptides differentially expressed in the serum of patients compared with healthy volunteers were identified by mass spectroscopy.. A pattern of proteins/peptides consisting of four protein/peptide peaks at m/z 1467, 1867, 2701, and 2094 was identified. These protein/peptide peaks were able to differentiate the studied populations with close to 100% sensitivity and specificity. Three of the deregulated proteins/peptides at m/z 1867, 2701, and 2094 were identified by mass spectroscopy (LTQ Orbitrap XL) as tubulin beta chain, thymosin beta-4-like protein 3, and cytochrome b-c₁ complex subunit 1, respectively.. The pattern of proteins/peptides identified in the present work shows great potential for GC diagnosis. Deregulated proteins of tubulin beta chain, thymosin beta-4-like protein 3, and cytochrome b-c₁ complex subunit 1 may be involved in the pathogenesis of GC and serve as potential serological diagnostic biomarkers.

Topics: Adenoma; Aged; Biomarkers, Tumor; Carrier Proteins; Case-Control Studies; Female; Gene Expression; Humans; Male; Mass Spectrometry; Middle Aged; Protein Isoforms; Sensitivity and Specificity; Stomach Neoplasms; Thymosin; Tubulin

Thymosin beta 4 (Tβ4) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation. Recently, a role for Tβ4 has been proposed in experimental and human carcinogenesis, including gastrointestinal cancer. This study was aimed at evaluating the relationship between Tβ4 immunoreactivity and the initial steps of carcinogenesis.. In total, 60 intestinal biopsies, including 10 hyperplastic polyps, 10 sessile serrated adenomas/polyps, 15 colorectal adenomas with low-grade dysplasia, 15 adenomas with high-grade dysplasia, 15 adenocarcinomas and 10 samples of normal colon mucosa, were analyzed for Tβ4 expression by immunohistochemistry.. Weak cytoplasmic reactivity for Tβ4 was detected in the normal colon mucosa. No reactivity for Tβ4 was found in hyperplastic and sessile serrated polyps/adenomas. Tβ4 expression was observed in 10/15 colorectal adenocarcinomas. In adenomas with low-grade dysplasia, Tβ4 immunoreactivity was mainly detected in dysplastic glands but was absent in hyperplastic glands. Tβ4 immunoreactivity was characterized by spot-like perinuclear staining. In high-grade dysplastic polyps, immunostaining for Tβ4 appeared diffuse throughout the entire cytoplasm of dysplastic cells. Spot-like perinuclear reactivity was detected in adenocarcinoma tumor cells.. Our study shows for the first time that Tβ4 is expressed during different steps of colon carcinogenesis. The shift of Tβ4 immunolocalization from low-grade to high-grade dysplastic glands suggests a role for Tβ4 in colorectal carcinogenesis. However, the real meaning of Tβ4 reactivity in dysplastic intestinal epithelium remains unknown.

Topics: Adenoma; Biopsy; Cell Differentiation; Colon; Colonic Neoplasms; Colonic Polyps; Disease Progression; Female; Humans; Immunohistochemistry; Male; Neoplasm Proteins; Thymosin

Forty pituitary adenomas were immunostained with an antibody raised against the C-terminal fragment (101-109) of human prothymosin alpha (PT alpha). The strong positive immunostaining was found in the subpopulation of cell nuclei and intratumoral vessel walls, while the cytoplasm of adenoma cells was slightly immunopositive. The significantly higher percentage of PT alpha-positive cell nuclei was found in recurrent pituitary adenomas as compared with primary tumors. However, there was no correlation between the percentage of PT alpha-positive cell nuclei and Ki-67 indices. Gonadotropinomas were characterized by higher nuclear PT alpha expression in comparison to other pituitary adenomas, which is probably linked with the high recurrence rate of these tumors. It is suggested that PT alpha immunostaining may be helpful in predicting the pituitary tumor recurrence. However, this conclusion needs to be confirmed in further prospective studies. Moreover, PT alpha may be also useful as an immunohistochemical marker of the intratumoral microvasculature.

Topics: Adenoma; Biomarkers, Tumor; Humans; Immunohistochemistry; Ki-67 Antigen; Pituitary Neoplasms; Protein Precursors; Recurrence; Thymosin

The ability of thymosin alpha1 (Talpha1) to prevent lung and breast cancer was investigated. Lung adenomas developed in A/J mice injected with carcinogens, such as urethane. The lung adenoma number was reduced by 15-45% if animals were daily treated subcutaneously (s.c.) with Talpha1 (0.4 mg/kg). Talpha1 (1 microM) directly inhibited the growth of mouse lung cell lines. These results suggest that Talpha1 may prevent mouse lung carcinogenesis because it directly inhibits the growth of lung cancer cells. Talpha1 prevented mammary carcinogenesis in two animal models. In the Fisher rat, an animal model of mammary cancer that is estrogen receptor dependent, tumors were initiated by the injection of N-methylurea (NMU). The rat survival was significantly increased by the daily injection of Talpha1. In the SV40T antigen mouse, a transgenic female mouse that spontaneously gets mammary cancer in an estrogen receptor-independent manner, survival was increased and tumor burden was significantly decreased by daily injection of Talpha1. These results indicate that Talpha1 is a chemopreventive agent in animal models for lung and breast carcinogenesis.

Topics: Adenoma; Animals; Anticarcinogenic Agents; Female; Lung Neoplasms; Mammary Neoplasms, Animal; Mice; Mice, Inbred A; Rats; Rats, Inbred F344; Thymalfasin; Thymosin

Transcription factors play an essential role in regulating both cell proliferation and programmed cell death. Proliferation and apoptosis-related transcription factor immunoexpression patterns were concomitantly investigated in tissue sections of normal thyroid, goiters, follicular adenomas and well-differentiated papillary and follicular carcinomas using antibodies against prothymosin alpha, E2F-1, p53, Bcl2, and Bax proteins. Proliferation and apoptotic indices were determined by Ki-67 immunoreactivity and the terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick-end labeling technique, respectively. Prothymosin alpha and E2F-1 immunoexpression levels were found to be significantly elevated in well-differentiated carcinomas compared to adenomas, goiters and normal tissues (P < 0.05). Both proteins were directly correlated with the proliferation index (P < 0.05). E2F-1 was additionally correlated with the apoptotic index (P < 0.05). The majority of cases were negative for p53 staining. Positive Bcl2 immunostaining was detected in all thyroid histotypes. None of the normal tissues showed Bax immunoreactivity, while positive accumulation differed significantly between hyperplastic and neoplastic histotypes. Direct correlations were observed between prothymosin alpha and Bcl2 as well as between E2F-1 and Bax immunoexpression (P < 0.05). These data demonstrate that prothymosin alpha and E2F-1 are strongly involved in the proliferation processes of thyroid neoplasias. Furthermore, prothymosin alpha may promote cell survival through the Bcl2 anti-apoptotic pathway, while E2F-1-induced apoptosis via p53-independent pathways may be associated with transcriptional activation of bax pro-apoptotic gene.

Topics: Adenoma; Adolescent; Adult; Aged; Apoptosis; bcl-2-Associated X Protein; Carcinoma, Papillary, Follicular; Cell Proliferation; DNA-Binding Proteins; E2F1 Transcription Factor; Female; Goiter; Humans; Immunohistochemistry; Male; Middle Aged; Protein Precursors; Repressor Proteins; Thymosin; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms; Transcription Factors; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

Overexpression of thymosin beta-10 (TB10) has been shown in rat thyroid transformed cell lines, and in human thyroid carcinoma tissues and cell lines. To investigate whether TB10 detection could be a valid tool in the diagnosis of human thyroid neoplasias, we extended the analysis of TB10 expression to a large number of thyroid hyperproliferative and neoplastic tissues using an immunohistochemical assay. Our analyses showed a TB10 positive staining in all human thyroid carcinomas particularly in the anaplastic histotypes, whereas no TB10 immunostaining was observed in normal thyroid, in adenomas and the majority of the goiters. These results suggest that the evaluation of TB10 gene expression may be considered a promising means of diagnosis of human thyroid hyperproliferative disorders.

Topics: Adenoma; Carcinoma; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Humans; Immunohistochemistry; Thymosin; Thyroid Gland; Thyroid Neoplasms

The effects of thymosin (THN) alpha1 were investigated using the urethane injection carcinogenesis A/J mouse model. Lung adenomas were observed 2.5, 3, and 4 months after urethane injection (400 mg/kg i.p.) into female A/J mice. Daily administration of THNalpha1 (0.4 mg/kg, s.c.) reduced lung adenoma multiplicity significantly, by approximately 45, 40, and 17%, respectively, 2.5, 3, and 4 months after urethane injection. Animals treated with THNalpha1 had a significantly greater white cell density than control A/J mice. Endogenous THNalpha1-like peptides were detected in the mouse lung. By radioimmunoassay and by Western blot, prothymosin alpha was detected in the mouse lung. By immunocytochemistry, THNalpha1-like peptides were detected in all lung compartments including the bronchus, adenoma, bronchioles, and alveoli. These results indicate that exogenous THNalpha1 prevents lung carcinogenesis in A/J mice.

Topics: Adenoma; Animals; Blood; Blotting, Western; Bronchi; Carcinogens; Female; Immunohistochemistry; Lung; Lung Neoplasms; Mice; Pulmonary Alveoli; Radioimmunoassay; Thymalfasin; Thymosin; Time Factors; Tissue Distribution; Urethane

Cytokines such as interleukin-1 (IL-1) and IL-6 stimulate the hypothalamic-pituitary-adrenal (HPA) axis. In addition, these proteins affect pituitary cell proliferation in vitro. Thymosin fraction 5 (TF5) is a partially purified preparation of the bovine thymus that enhances immune system functioning. Because TF5 similarly stimulates the HPA axis, we examined the effects of this preparation on neuroendocrine tumor cell proliferation. Cells of the PRL-secreting rat anterior pituitary adenoma, MMQ (5-50 x 10(3) cells/well), were exposed to vehicle (RPMI-1640 containing 2.5% FCS, 7.5% horse serum, and antibiotics) or TF5 (100-500 microg/ml) for up to 96 h and the proliferation of MMQ cells monitored using the MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide). TF5-mediated inhibition of cell proliferation was dependent on both TF5 concentration and the initial MMQ cell number. Minimal reductions in optical densities resulted from exposure to 100 microg/ml TF5, whereas the highest concentration of this preparation (i.e. 500 microg/ml) completely blocked MMQ cell division. The concentration-dependent effects of TF5 were particularly striking at initial plating densities of 25 and 50 x 10(3) MMQ cells/well; in contrast, all concentrations of TF5 completely inhibited MMQ cell growth at 5 and 10 x 10(3) cells/well. The antiproliferative actions of TF5 on MMQ cells were demonstrable within 24 h and remained for up to 96 h as determined by the MTT assay and actual cell counts. Because the highest densities of MMQ cells were partially refractive to the antiproliferative effects of TF5, we examined the effects of PRL (1-1000 nM) and MMQ cell conditioned medium (50%) on TF5 inhibition of MMQ adenoma proliferation. The TF5 concentration-dependent inhibition of MMQ cell growth was largely reversed by the 50% conditioned medium, whereas PRL slightly potentiated the antiproliferative actions of TF5. The proliferation of the rat C6 glioma cell line (10-30 x 10(3) cells/well) demonstrated greater sensitivity to TF5: concentrations as low as 10 microg/ml TF5 inhibited C6 cell proliferation (P < 0.01), and near-maximal inhibition was noted at 200 microg/ml TF5. Significant reductions in MMQ and C6 cell viabilities accompanied decreases in cell number and morphological analysis indicated these cells were dying by apoptosis. The peptides thymosin alpha1 (T alpha1), thymosin beta4 (T beta4), MB35, and MB40 had no effect on either MMQ or C6 cell proliferat

Topics: Adenoma; Animals; Apoptosis; Cattle; Cell Division; Cell Survival; Chromatography, High Pressure Liquid; Glioma; Pituitary Neoplasms; Rats; Thymosin; Tumor Cells, Cultured

Identification of gene products exclusively or abundantly expressed in cancer may yield novel tumour markers. We recently isolated a number of cDNA clones, including alpha-prothymosin, from rat hepatocellular carcinoma (HCC) using a subtraction-enhanced display technique. Alpha-Prothymosin is involved in cell proliferation and is regulated by the oncogene c-myc in vitro. In the present study, we analysed alpha-prothymosin gene expression and its correlation with c-myc in patients with HCC, cirrhosis and adenoma and in normal controls. Hepatic alpha-prothymosin messenger RNA (mRNA) levels were two- to 9.2-fold higher in tumoral tissues than in adjacent non-tumoral tissues in 14 of 17 patients with HCC, regardless of coexisting cirrhosis and viral hepatitis. No marked difference in alpha-prothymosin mRNA levels was present in patients with adenoma and hepatic cirrhosis and in healthy controls. The c-myc mRNA amounts were two- to fivefold increased in 11 of 17 patients with HCC and correlated significantly with those of alpha-prothymosin (P < 0.001). In situ hybridization revealed that increased alpha-prothymosin mRNA was localized in the tumour nodules of the patients with HCC. These data suggest that overexpression of alpha-prothymosin in HCC patients, correlated with c-myc, is possibly involved in the tumorigenic process and may be a novel molecular marker for human HCC.

Topics: Adenoma; Adult; Aged; Biomarkers, Tumor; Blotting, Northern; Carcinoma, Hepatocellular; Female; Hepatitis B; Hepatitis C; Humans; In Situ Hybridization; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Protein Precursors; Proto-Oncogene Proteins c-myc; Radioimmunoassay; RNA, Messenger; Thymosin