thymosin and Cell-Transformation--Neoplastic

Thymosin β4 (Tβ4), a 5 kDa protein, has been demonstrated to play an important role in a variety of biological activities, such as actin sequestering, cellular motility, migration, inflammation, and damage repair. Recently, several novel findings provided compelling evidence that Tβ4 played a key role in facilitating tumor metastasis and angiogenesis. It has been found that Tβ4 expressed increasingly in a number of metastatic tumors, which was associated with an increased expression of a known angiogenic factor, vascular endothelial growth factor. Thus, Tβ4 provided a potential target of opportunity for cancer management, especially for cancer metastasis therapy.

Topics: Animals; Cell Movement; Cell Survival; Cell Transformation, Neoplastic; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Neoplasm Metastasis; Neoplastic Stem Cells; Neovascularization, Pathologic; Thymosin; Wound Healing

Prothymosin alpha is an extremely abundant nuclear oncoprotein-transcription factor essential for cell cycle progression and proliferation that has been recently suggested as an anti- apoptotic factor. Similarly to other oncoproteins, prothymosin alpha is overexpressed in a variety of cancer tissues and cell lines. The present review highlights on the proliferation and anti-apoptotic properties of prothymosin alpha and its possible role in cancer development.

Topics: Animals; Apoptosis; Cell Proliferation; Cell Transformation, Neoplastic; Humans; Models, Biological; Protein Precursors; Thymosin

Male breast cancer comprises less than 1% of breast cancer diagnoses. Although estrogen exposure has been causally linked to the development of female breast cancers, the etiology of male breast cancer is unclear. Here, we show via fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two independent cohorts of male breast cancer patients. We also show somatic loss of the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of loss at this locus in male breast cancers. To further understand the function of TMSB4Y, we created inducible cell lines of TMSB4Y in the female human breast epithelial cell line MCF-10A. Expression of TMSB4Y resulted in aberrant cellular morphology and reduced cell proliferation, with a corresponding reduction in the fraction of metaphase cells. We further show that TMSB4Y interacts directly with β-actin, the main component of the actin cytoskeleton and a cell cycle modulator. Taken together, our results suggest that clonal loss of the Y chromosome may contribute to male breast carcinogenesis, and that the TMSB4Y gene has tumor suppressor properties.

Topics: Actins; Breast Neoplasms, Male; Cell Line; Cell Proliferation; Cell Shape; Cell Transformation, Neoplastic; Chromosomes, Human, Y; Female; Gene Deletion; Gene Expression Regulation, Neoplastic; Humans; In Situ Hybridization, Fluorescence; Male; Mammary Glands, Human; Phenotype; Polymerase Chain Reaction; Thymosin; Time Factors; Transfection; Tumor Suppressor Proteins

Thymosin beta-4 (Tβ4) is known to be involved in tumorigenesis. Overexpression of this polypeptide has been observed in a wide variety of cancers, including colorectal carcinoma (CRC). Accordingly, Tβ4 has been proposed to be a novel therapeutic target for CRC, especially in its metastatic form. Although in vitro tumor-suppressive effects of Tβ4 gene silencing mediated by small hairpin RNA (shRNA) have already been demonstrated, the in vivo efficacy of such an approach has not yet been reported. Herein, we demonstrated that infection with recombinant adenovirus expressing an shRNA targeting Tβ4 markedly reduced the growth of and robustly induced apoptosis in CT-26 mouse CRC cells in culture. Additionally, tumors grown in nude mice from the CT-26 cells whose Tβ4 expression already been downregulated by virus infection were also drastically reduced. Most importantly, significant growth arrest of tumors derived from the parental CT-26 cells was observed after multiple intratumoral injections of these viruses. Together, our results show for the first time that in vivo silencing of Tβ4 expression by its shRNA generated after adenoviral infection can suppress CRC growth. These results further demonstrate the feasibility of treating CRC by a Tβ4 knockdown gene therapeutic approach.

Topics: Actins; Adenoviridae; Animals; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Transformation, Neoplastic; Colorectal Neoplasms; Disease Models, Animal; Gene Knockout Techniques; Genetic Vectors; Humans; Mice; RNA Interference; RNA, Messenger; RNA, Small Interfering; Thymosin; Transduction, Genetic; Tumor Burden; Xenograft Model Antitumor Assays

Thymosin β 4 (Tβ(4)) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation during embryogenesis. Recently, a role for Tβ(4) has been proposed in experimental and human carcinogenesis. This study was aimed at evaluating the correlation between Tβ(4) immunoractivity and colorectal cancer, with particular attemption to tumor cells undergoing epithelial-mesenchymal transition.. 86 intestinal biopsies were retrospectively analyzed including 76 colorectal adenocarcinomas with evident features of epithelial-mesenchymal transition, and 10 samples of normal colorectal mucosa. Paraffin sections were immunostained for Tβ(4) and for E-cadherin. Total RNA was isolated from frozen specimens obtained, at surgery, from the normal colon mucosa, the deeper regions and the superficial tumor regions in four cases of colon cancer. Tβ(4) immunoreactivity was detected in the vast majority (59/76) of colon carcinomas, showing a patchy distribution, with well differentiated areas significantly more reactive than the less differentiated tumor zones. We also noted a zonal pattern in the majority of tumors, characterized by a progressive increase in immunostaining for Tβ(4) from the superficial toward the deepest tumor regions. The strongest expression for Tβ(4) was frequently detected in invading tumor cells with features of epithelial-mesenchymal transition. The increase in reactivity for Tβ(4) matched with a progressive decrease in E-cadherin expression in invading cancer cells. At mRNA level, the differences in Tβ(4) expression between the surrounding colon mucosa and the tumors samples were not significant.. Our data show that Tβ(4) is expressed in the majority of colon cancers, with preferential immunoreactivity in deep tumor regions. The preferential expression of the peptide and the increase in intensity of the immunostaining at the invasion front suggests a possible link between the peptide and the process of epithelial mesenchymal transition, suggesting a role for Tβ(4) in colorectal cancer invasion and metastasis.

Topics: Adenocarcinoma; Cadherins; Cell Differentiation; Cell Line, Tumor; Cell Transformation, Neoplastic; Cohort Studies; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Humans; Immunohistochemistry; Thymosin

Oxidative stress, perturbations in the cellular thiol level and redox balance, affects many cellular functions, including signaling pathways. This, in turn, may cause the induction of autophagy or apoptosis. The NRF2/KEAP1 signaling pathway is the main pathway responsible for cell defense against oxidative stress and maintaining the cellular redox balance at physiological levels. The relation between NRF2/KEAP1 signaling and regulation of apoptosis and autophagy is not well understood. In this hypothesis article we discuss how KEAP1 protein and its direct interactants (such as PGAM5, prothymosin α, FAC1 (BPTF), and p62) provide a molecular foundation for a possible cross-talk between NRF2/KEAP1, apoptosis, and autophagy pathways. We present a hypothesis for how NRF2/KEAP1 may interfere with the cellular apoptosis-regulatory machinery through activation of the ASK1 kinase by a KEAP1 binding partner-PGAM5. Based on very recent experimental evidence, new hypotheses for a cross-talk between NF-κB and the NRF2/KEAP1 pathway in the context of autophagy-related "molecular hub" protein p62 are also presented. The roles of KEAP1 molecular binding partners in apoptosis regulation during carcinogenesis and in neurodegenerative diseases are also discussed.

Topics: Adaptor Proteins, Signal Transducing; Amino Acid Motifs; Animals; Antigens, Nuclear; Apoptosis; Autophagy; Carrier Proteins; Cell Transformation, Neoplastic; Gene Expression Regulation; Humans; Intracellular Signaling Peptides and Proteins; Kelch-Like ECH-Associated Protein 1; MAP Kinase Kinase Kinase 5; Mitochondrial Proteins; Nerve Tissue Proteins; Neurodegenerative Diseases; NF-E2-Related Factor 2; NF-kappa B; Oxidation-Reduction; Oxidative Stress; Phosphoprotein Phosphatases; Phosphorylation; Protein Binding; Protein Precursors; Reactive Oxygen Species; Sequestosome-1 Protein; Signal Transduction; Sulfhydryl Compounds; Thymosin; Transcription Factors; Ubiquitination

Lung cancer is the leading cause of cancer-related deaths worldwide and is usually associated with a late diagnosis and a poor prognosis. Thymosin β(10) (TMSB10) is a monomeric actin sequestering protein that regulates actin cytoskeleton organization. The aberrant TMSB10 expression has been implicated in the pathogenesis of human cancers. However, its role in carcinogenesis is still controversial. To better understand the role of TMSB10 in lung tumorigenesis and its regulatory mechanism, we examined the methylation status and expression of the TMSB10 gene in non-small cell lung cancers (NSCLCs) using methylation-specific PCR (MSP) and immunohistochemistry (IHC), respectively. MSP analysis showed that the TMSB10 promoter was already unmethylated in most tumor tissues and became demethylated in 20 (14.4%) of the 139 NSCLCs. TMSB10 hypomethylation was not significantly correlated with the clinicopathological features. IHC showed that the TMSB10 protein was strongly expressed in the cytoplasm of malignant cells and its overexpression was detected in 50.0% of the tumor tissues compared to normal tissues. TMSB10 overexpression was frequently observed in sqaumous cell carcinomas compared to adenocarcinomas with border line significance (P = 0.072). However, TMSB10 methylation status was not linked to its overexpression. Collectively, these results suggest that TMSB10 hypomethylation may be a frequent event in NSCLCs, but it may not be a common mechanism underlying TMSB10 overexpression. However, further studies with large numbers of patients are needed to confirm our findings.

Topics: Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Transformation, Neoplastic; Disease Progression; DNA Methylation; Female; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Neoplasm Staging; Promoter Regions, Genetic; Survival Analysis; Thymosin; Up-Regulation

Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO(2)) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO(2), either uncoated (TiO(2)-1, hydrophilic) or coated with stearic acid (TiO(2)-2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO(2)-1, but not TiO(2)-2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO(2)-1 and TiO(2)-2 treatments. However, TiO(2)-2, but not TiO(2)-1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO(2)-1 and TiO(2)-2 resulted in intracellular ROS formation, TiO(2)-2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO(2)-2, but not TiO(2)-1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO(2) toxicity acquired a tumorigenic phenotype. TiO(2)-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO(2) has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cell Line, Tumor; Cell Transformation, Neoplastic; Cytokines; Deoxyguanosine; Dinoprostone; Female; Fibrosarcoma; Intercellular Signaling Peptides and Proteins; Mice; Mice, Inbred C57BL; Nanoparticles; Neoplasm Invasiveness; Particle Size; Reactive Oxygen Species; Thymosin; Titanium; Vascular Endothelial Growth Factor A

S-adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the synthesis of polyamines essential for cell growth and proliferation. Its overexpression induces the transformation of murine fibroblasts in both sense and antisense orientations, yielding highly invasive tumors in nude mice. These cell lines hence provide a good model to study cell invasion. Here, the gene expression profiles of these cells were compared with their normal counterpart by microarray analyses (Incyte Genomics, Palo Alto, CA, and Affymetrix, Santa Clara, CA). Up-regulation of the actin sequestering molecule thymosin beta4 was the most prominent change in both cell lines. Tetracycline-inducible expression of thymosin beta4 antisense RNA caused a partial reversal of the transformed phenotype. Further, reversal of transformation by dominant-negative mutant of c-Jun (TAM67) caused reduction in thymosin beta4 mRNA. Interestingly, a sponge toxin, latrunculin A, which inhibits the binding of thymosin beta4 to actin, was found to profoundly affect the morphology and proliferation of the AdoMetDC transformants and to block their invasion in three-dimensional Matrigel. Thus, thymosin beta4 is a determinant of AdoMetDC-induced transformed phenotype and invasiveness. Up-regulation of thymosin beta4 was also found in ras-transformed fibroblasts and metastatic human melanoma cells. These data encourage testing latrunculin A-like and other agents interfering with thymosin beta4 for treatment of thymosin beta4-overexpressing tumors with high invasive and metastatic potential.

Topics: Adenosylmethionine Decarboxylase; Animals; Cell Transformation, Neoplastic; Fibroblasts; Gene Expression Profiling; Humans; Melanoma; Mice; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; Phenotype; Skin Neoplasms; Thymosin; Up-Regulation

Rhabdomyosarcomas (RMS) are highly aggressive tumors that are thought to arise as a consequence of the regulatory disruption of the growth and differentiation of skeletal muscle progenitor cells. Normal myogenesis is characterized by the expression of the myogenic regulatory factor gene family but, despite their expression in RMS, these tumor cells fail to complete the latter stages of myogenesis. The RMS cell line RD-A was treated with 12-O-tetradecanoylphorbol-13-acetate to induce differentiation and cultured for 10 days. RNA was extracted on days 1, 3, 6, 8 and 10. A human skeletal muscle cDNA microarray was developed and used to analyze the global gene expression of RMS tumors over the time-course of differentiation. As a comparison, the genes identified were subsequently examined during the differentiated primary human skeletal muscle cultures. Prothymosin alpha (PTMA), and translocase of inner mitochondrial membrane 10 (Tim10), two genes not previously implicated in RMS, showed reduced expression during differentiation. Marked differences in the expression of PTMA and Tim10 were observed during the differentiation of human primary skeletal muscle cells. These results identify several new genes with potential roles in the myogenic arrest present in rhabdomyosarcoma. PTMA expression in RMS biopsy samples might prove to be an effective diagnostic marker for this disease.

Topics: Adult; Cell Line, Tumor; Cell Transformation, Neoplastic; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Membrane Proteins; Mitochondrial Precursor Protein Import Complex Proteins; Muscle, Skeletal; Oligonucleotide Array Sequence Analysis; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; Rhabdomyosarcoma; RNA, Messenger; RNA, Neoplasm; Saccharomyces cerevisiae Proteins; Soft Tissue Neoplasms; Tetradecanoylphorbol Acetate; Thymosin

Topics: Apoptosis; Caspase 3; Caspase 9; Caspases; Cell Transformation, Neoplastic; Enzyme Activation; Humans; Mitochondria; Neoplasms; Protein Precursors; Pyridines; RNA Interference; Thymosin; Tumor Suppressor Proteins

Topics: Actins; Animals; Antineoplastic Agents; Cell Physiological Phenomena; Cell Transformation, Neoplastic; Humans; Male; Melanoma, Experimental; Neoplasm Metastasis; Neovascularization, Pathologic; Prostatic Neoplasms; Thymosin; Up-Regulation

The effects of thymosin alpha1 (Talpha1) on mammary carcinogenesis was investigated in Fisher rats. Mammary carcinomas were observed 3 months after N-nitrosomethylurea (NMU) injection (10mg, i.p.) into Fisher rats. Daily administration of Talpha1 (10 microg, s.c.) reduced mammary carcinoma incidence and prolonged survival time. Animals treated with exogenous Talpha1 had a significantly greater blood white cell density than control Fisher rats. These results suggest that Talpha1 prevents mammary carcinoma incidence as a result of stimulation of the immune system.

Topics: Animals; Blood Chemical Analysis; Cell Transformation, Neoplastic; Female; Leukocyte Count; Mammary Neoplasms, Experimental; Methylnitrosourea; Rats; Rats, Inbred F344; Thymalfasin; Thymosin

Prothymosin alpha (ProTalpha), a cellular molecule known to be associated with cell proliferation, is transcriptionally up-regulated on expression of c-myc and interacts with histones in vitro and associates with histone H1 in cells. Previous studies have also shown that ProTalpha is involved in chromatin remodeling. Recent studies have shown that ProTalpha interacts with the acetyl transferase p300 and an essential Epstein-Barr virus protein, EBNA3C, involved in regulation of viral and cellular transcription. These studies suggest a potential involvement in regulation of histone acetylation through the association with these cellular and viral factors. In the current studies, we show that heterologous expression of ProTalpha in the Rat-1 rodent fibroblast cell line results in increased proliferation, loss of contact inhibition, anchorage-independent growth, and decreased serum dependence. These phenotypic changes seen in transfected Rat-1 cells are similar to those observed with a known oncoprotein, Ras, expressed under the control of a heterologous promoter and are characteristic oncogenic growth properties. These results demonstrate that the ProTalpha gene may function as an oncogene when stably expressed in Rat-1 cells and may be an important downstream cellular target for inducers of cellular transformation, which may include Epstein-Barr virus and c-myc.

Topics: Animals; Base Sequence; Cell Line; Cell Transformation, Neoplastic; DNA Primers; Fibroblasts; Oncogene Proteins; Promoter Regions, Genetic; Protein Precursors; Rats; Thymosin; Transfection

The tumor suppressor Bin1 was identified through its interaction with the N-terminal region of Myc which harbors its transcriptional activation domain. Here we show that Bin1 and Myc physically and functionally associate in cells and that Bin1 inhibits cell proliferation through both Myc-dependent and Myc-independent mechanisms. Bin1 specifically inhibited transactivation by Myc as assayed from artificial promoters or from the Myc target genes ornithine decarboxylase (ODC) and alpha prothymosin (pT). Inhibition of ODC but not pT required the presence of the Myc binding domain (MBD) of Bin1 suggesting two mechanisms of action. Consistent with this possibility, a non-MBD region of Bin1 was sufficient to recruit a repression function to DNA that was unrelated to histone deacetylase. Regions outside the MBD required for growth inhibition were mapped in Ras cotransformation or HepG2 hepatoma cell growth assays. Bin1 required the N-terminal BAR domain to suppress focus formation by Myc whereas the C-terminal U1 and SH3 domains were required to inhibit adenovirus E1A or mutant p53, respectively. All three domains contributed to Bin1 suppression of tumor cell growth but BAR-C was most crucial. These findings supported functional interaction between Myc and Bin1 in cells and indicated that Bin1 could inhibit malignant cell growth through multiple mechanisms.

Topics: Adaptor Proteins, Signal Transducing; Adenovirus E1A Proteins; Animals; Binding Sites; Carrier Proteins; Cell Division; Cell Line; Cell Transformation, Neoplastic; Humans; Nuclear Proteins; Ornithine Decarboxylase; Promoter Regions, Genetic; Protein Binding; Protein Precursors; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins p21(ras); Repressor Proteins; Response Elements; Sequence Deletion; src Homology Domains; Thymosin; Transcriptional Activation; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the specific DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin and Cdc25A. In this study we examined the involvement of c-Myc target genes in human oncogenesis induced by c-myc or N-myc. In MCF-7 breast cancer cells, the induction of c-myc expression by estrogen was followed by the induction of all the Myc targets that we examined, indicating that those genes can serve as c-Myc targets in human oncogenesis. Moreover, in breast tumors exhibiting c-myc overexpression, several Myc targets were also overexpressed. A clear correlation between the expression of c-myc and its targets was also detected in Burkitt's lymphomas, which involve a specific translocation of c-myc gene, but not in other lymphoma cells. Yet, in cells derived from a neuronal origin the pattern of expression of Myc targets was more complex. In a neuroepithelioma cell line that overexpresses c-myc, only some targets were expressed. In addition in neuroblastomas, in which N-myc is amplified and overexpressed, only ODC was overexpressed in all cell lines, while all other target genes were expressed in only some of the cell lines. The more complex expression pattern found for the Myc targets in neuroblastomas suggests that genes that were identified originally as targets for c-Myc regulation may be regulated by N-Myc, but other cell specific factors are also needed for transcription of the target genes.

Topics: Breast Neoplasms; Burkitt Lymphoma; cdc25 Phosphatases; Cell Transformation, Neoplastic; Estradiol; Female; Gene Expression Regulation, Neoplastic; Humans; Neuroblastoma; Neuroectodermal Tumors, Primitive, Peripheral; Ornithine Decarboxylase; Protein Precursors; Protein Tyrosine Phosphatases; Proteins; Proto-Oncogene Proteins c-myc; Thymosin; Transaminases

Transcriptional activation by c-Myc through specific E box elements is thought to be essential for its biological role. However, c-MycS is unable to activate transcription through these elements and yet retains the ability to stimulate proliferation, induce anchorage-independent growth, and induce apoptosis. In addition, c-MycS retains the ability to repress transcription of several specific promoters. Furthermore, c-MycS can rescue the c-myc null phenotype in fibroblasts with homozygous deletion of c-myc. Taken together, our data argue against the paradigm that all of the biological functions of c-Myc are mediated by transcriptional activation of specific target genes through E box elements.

Topics: 3T3 Cells; Animals; Apoptosis; Cell Division; Cell Line; Cell Transformation, Neoplastic; Enhancer Elements, Genetic; GADD45 Proteins; Gene Expression Regulation; Genes, myc; Genes, p53; Intracellular Signaling Peptides and Proteins; Membrane Glycoproteins; Mice; Ornithine Decarboxylase; Phenotype; Protein Isoforms; Protein Precursors; Proteins; Proto-Oncogene Proteins c-myc; Rats; Repressor Proteins; Response Elements; Saccharomyces cerevisiae Proteins; Sequence Deletion; Thymosin; Transcriptional Activation; Transfection

Thymosin alpha 1 (T alpha 1) is an immune modulatory peptide which has been evaluated in a variety of clinical trials. Although no in vivo adverse effects, including enhancement of tumor growth, have been noted, in vitro studies suggesting a role for T alpha 1 in cell growth have been reported. The studies presented in this report evaluated both exogenously added T alpha 1 and endogenously expressed T alpha 1 as factors which could either promote growth of tumor cells or induce transformation. No effect of exogenous T alpha 1 on cell growth was found. NIH-3T3 cells transfected with cDNA for the precursor ProThymosin alpha (Pro T alpha) expressed elevated levels of authentic T alpha 1 but did not demonstrate either enhanced proliferation in liquid culture or transformation as defined by the loss of contact inhibition or anchorage independent growth in soft agar. Thus these studies argue against the hypothesis that T alpha 1 is either an intracellular or extracellular growth promoter.

Topics: 3T3 Cells; Adenocarcinoma; Animals; Breast Neoplasms; Cecal Neoplasms; Cell Division; Cell Transformation, Neoplastic; Colonic Neoplasms; Growth Substances; Ileal Neoplasms; Mice; Protein Precursors; Thymosin; Tumor Cells, Cultured

The preparations of alpha 1-thymosin (T), alpha-tumor necrotic factor (TNF) and their based hybrid proteins: T-TNF, TNF-T, and T-TNF-T were studied by using a wide spectrum of immunobiological tests. In the L-929 cells, T-TNF preserved cytotoxicity unique to TNF; TNF-T preserved it 10 times less, and T-NTF-T was completely inactive. TNF-T inhibited the growth of Molt-4, Jm-9, Raji cells by 63 = 84%, and TNF suppressed only Raji cells by 50%. Hybrid proteins caused cell proliferation of the thymus, spleen, and lymph nodes; H-2K, CD4, and CD8 differently increased the expression of thymocytic antigens. The authors found the different effects of the drugs on phagocytosis, the production of antibody-forming cells, delayed reaction, and activation of natural killer cells. The protein T-TNF-T produced the most pronounced action.

Topics: Animals; Antibody Formation; Biomarkers, Tumor; CD4-CD8 Ratio; Cell Division; Cell Line, Transformed; Cell Transformation, Neoplastic; Humans; Lymph Nodes; Lymphocyte Activation; Macrophages; Mice; Phagocytosis; Spleen; Thymalfasin; Thymosin; Thymus Gland; Tumor Necrosis Factor-alpha

Acute lymphoblastic leukemia was observed in a 64-year-old male patient with 50-80% hand-mirror cells in the peripheral blood and in the bone marrow. Immunologic surface marker tests indicated that the cells were non-T non-B lymphocytes; however, the addition of thymosin (fraction V) to the bone marrow cells induced the capability of mounting a positive local xenogeneic graft-versus-host reaction (GVHR), demonstrating the pre-T-cell lineage of the hand-mirror cells in this patient.

Topics: Animals; Bone Marrow; Cell Differentiation; Cell Transformation, Neoplastic; Graft vs Host Reaction; Humans; Leukemia, Lymphoid; Male; Middle Aged; Rats; Rosette Formation; T-Lymphocytes; Thymosin

The effect of thymosin on suppressor-cell function was evaluated in vivo in a murine tumor system and in vitro on human lymphocytes. In mice, the Lewis tumor system was used. We showed that splenocytes from tumor-bearing animals were able to enhance tumor growth in a syngeneic system. This enhancement was similar when thymocytes from tumor-bearing animals were used and disappeared after anti-Thy 1-2 antiserum treatment, suggesting a T-dependence. Treatment of the tumor-growth-enhancing lymphocytes with corticosteroids or irradiation caused this effect to disappear completely suggesting that the tumor-growth-enhancing T-lymphocytes were suppressor T-cells. Furthermore thymosin (fraction 5)-treated, tumor-growth-enhancing T-lymphocytes were not able to enhance tumor growth and even significantly decreased it. In the human system we showed that Con A-stimulated lymphocytes were able to suppress the response of normal lymphocytes to PHA, PWM, and Con A, and in MLC. This effect was significantly blocked in presence of thymosin fraction 5.

Topics: Animals; Cell Transformation, Neoplastic; Cells, Cultured; Concanavalin A; Humans; Immune Sera; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Phytohemagglutinins; Spleen; T-Lymphocytes; Thymosin; Thymus Hormones