Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

Papanastasiou, Marilena; Baxevanis, Constantin N.; Papamichail, Michael

doi:10.1007/bf01741862

Cited by 34 publications

(27 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SpeciWcally, therapeutic administration of proT (ca. 3 g/ mouse over 3 weeks) in DBA/2 mice inoculated with syngeneic leukemic L1210 cells inhibited the development of ascites in 20% of the animals and prolonged the survival of 40-60% of them by several weeks compared to controls (10 vs 2 weeks, respectively) [72]. A potential mechanism of action of the polypeptide was linked to the activation of peritoneal exudate cells in proT -treated mice, since they were shown to produce six to eight times higher levels of tumor necrosis factor (TNF)-and thus exhibit cytotoxicity against various cell lines, both TNF--sensitive and TNF--resistant.…”

Section: A-thymosins In Cancer Therapymentioning

confidence: 91%

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

Ioannou

Samara

Livaniou

et al. 2012

Cancer Immunol Immunother

View full text Add to dashboard Cite

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as "thymic hormones," are produced by this gland. Although the majority of them have not been proven to be thymus-specific, thymic peptides comprise an effective group of regulators, mediating important immune functions. Thymosin fraction five (TFV) was the first thymic extract shown to stimulate lymphocyte proliferation and differentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin α (proTα) and thymosin α1 (Tα1) showed that they are of clinical significance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeficiencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their effect are yet not fully elucidated, proTα and Tα1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proTα, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of Tα1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proTα into the clinical setting.

show abstract

Section: A-thymosins In Cancer Therapymentioning

confidence: 91%

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

Ioannou

Samara

Livaniou

et al. 2012

Cancer Immunol Immunother

View full text Add to dashboard Cite

show abstract

“…Perhaps, the most outstanding in vivo assays are the ones showing an anticancer activity for ProTa in an experimental tumour model, prolonging the survival of DBA/2 mice inoculated intraperitoneally with syngenic L1210 leukemic cells [24,25]. In vitro, ProTa has been shown to increase allo-and auto-mixed lymphocyte responses in multiple sclerosis and systemic lupus erythematosus patients [26,27].…”

Section: Introductionmentioning

confidence: 98%

Prothymosin alpha-receptor associates with lipid rafts in PHA-stimulated lymphocytes

Salgado

Piñeiro

Canda-Sánchez

et al. 2005

Molecular Membrane Biology

View full text Add to dashboard Cite

Lipid rafts are specialized plasma membrane microdomains in which glycosphingolipids and cholesterol are major structural components. Their relative insolubility to nonionic detergents is the most widely used method to purify these structures. Several signalling proteins are associated with these microdomains in T lymphocytes, including receptors for growth factors and cytokines. ProTalpha is a highly conserved and widely distributed protein whose physiological functions remain elusive. In previous works we identified, by means of affinity cross-linking, affinity chromatography and fluorescence microscopy, a set of binding proteins for ProTalpha in human lymphoblasts. Now, this work goes deeply in that ProTalpha receptor description revealing, by different experimental approaches, its presence in lipid rafts. Moreover, our results fit a model in which a tyrosine phosphorylation signalling cascade confined to rafts is initiated upon ProTalpha receptor recognition, which represents an important and promising finding in the research for elucidating the molecular mechanisms underlying the immunomodulatory functions of ProTalpha.

show abstract

“…In an experimental tumor model, animals pretreated with prothymosin ␣ prolonged their survival in 40 to 60% of cases. Prothymosin ␣ induces tumoricidal peritoneal macrophages, natural killer (NK) cells, lymphokine-activated killer activity in splenocytes, production of interleukin-2 and tumor necrosis factor alpha, and tumor-specific cytotoxic (CD8 ϩ ) and helper (CD4 ϩ ) T-cell activation when administered simultaneously with tumoral cells (2,3,35).…”

Section: Discussionmentioning

confidence: 99%

Boosting Immune Response to Hepatitis B DNA Vaccine by Coadministration of Prothymosin α-Expressing Plasmid

Yan-wen¹,

Cao²,

Li³

et al. 2005

Clin Vaccine Immunol

View full text Add to dashboard Cite

DNA vaccines induce protective humoral and cell-mediated immune responses in several animal models. However, compared to conventional vaccines, DNA vaccines usually induce poor antibody responses. In this study, we report that coadministration of a hepatitis B virus (HBV) DNA vaccine with prothymosin ␣ as an adjuvant improves antibody responses to HBV S antigen. We also observed higher seroconversion rates and higher antibody titers. Prothymosin ␣ appears to increase the number and affinity of hepatitis B surface antigen-specific, gamma interferon-secreting T cells and to enhance cellular immune response to the PreS2S DNA vaccine. Interestingly, administering the DNA separately from the prothymosin ␣ plasmid abrogated the enhancement of DNA vaccine potency. The results suggest that prothymosin ␣ may be a promising adjuvant for DNA vaccines.Immunization with naked DNA can be defined as the in vivo delivery of an antigen-encoding expression vector into a given tissue for the purpose of the induction of immune responses. This novel immunization approach results in de novo production of correctly folded and glycosylated protein antigens and in certain respects mimics the actions of live attenuated or recombinant virus vaccines. As a consequence, this mode of immunization may mimic natural infection and induce protective immune responses. In animal models, such genetic immunization induces both humoral and cellular immune responses against a range of viral pathogens, such as hepatitis B virus (31), influenza A virus (37, 43), herpes simplex virus (5, 27, 28), rabies virus (48), and human immunodeficiency virus type 1 (6, 45). In spite of the existence of safe and efficacious vaccines, hepatitis B virus (HBV) infection is one of the most common infectious diseases, with an estimated 350 million chronic HBV carriers worldwide (12,22). Patients with chronic hepatitis B are at high risk of developing liver cirrhosis, which is associated with a high rate of mortality due to the development of hepatocellular carcinoma or noncarcinomatous complications of cirrhosis (portal hypertension and liver failure) (19). In addition, these chronically HBV-infected carriers represent a reservoir of HBV. Prophylactic immunization against HBV infections can be achieved with recombinant subunit HBV vaccines (10, 30, 44); however, a small number of individuals do not develop protective immunity even after more than the recommended three hepatitis B surface antigen (HBsAg) inoculations. The incidence of nonresponse in immunocompetent young adults is around 5% but increases up to 30% with age of vaccination or even more in immunocompromised individuals (32). Other problems arising from the use of current HBV vaccines are escape variants with mutations within HBsAg and the requirement of at least three injections to achieve protection. For control of HBV infections and liver disease, efficacious but inexpensive DNA vaccines may thus be promising tools (18). Recent reports have demonstrated the efficacy of DNA-based HBV vaccines. Immunization ...

show abstract

Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

Cited by 34 publications

References 21 publications

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

Prothymosin alpha-receptor associates with lipid rafts in PHA-stimulated lymphocytes

Boosting Immune Response to Hepatitis B DNA Vaccine by Coadministration of Prothymosin α-Expressing Plasmid

Contact Info

Product

Resources

About