Thymosin α1 as a Chemopreventive Agent in Lung and Breast Cancer

Moody, Terry W.

doi:10.1196/annals.1415.040

Cited by 30 publications

(24 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, several studies have reported that Ta1 is capable of down-regulating the growth of cancer cells, such as murine B16 melanoma [42], lung cancer [43][44][45] and breast cancer [45]. However, the effect of Ta1 is pleiotropic, and it is usually used in combination with cytokines and chemotherapeutic agents in the treatment of cancers.…”

Section: Discussionmentioning

confidence: 99%

A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects

Lao

et al. 2015

Apoptosis

View full text Add to dashboard Cite

Thymosin alpha 1 (Tα1) is commonly used for treating several diseases; however its usage has been limited because of poor penetration of the target tissue, such as tumor cells. In the present study, Tα1-iRGD, a peptide by conjugating Tα1 with the iRGD fragment, was evaluated its performance in MCF-7 and MDA-MB-231 human breast cancer cells. Compared with the wild-type peptide, Tα1-iRGD was more selective in binding tumor cells in the cell attachment assay. Furthermore, the MTT assay confirmed that Tα1-iRGD proved more effective in significantly inhibiting the growth of MCF-7 cells in contrast to the general inhibition displayed by Tα1. Further, conjugation of Tα1 with iRGD preserved the immunomodulatory activity of the drug by increasing the proliferation of mouse spleen lymphocytes. Further, compared with Tα1 treatment, Tα1-iRGD treatment of MCF-7 cells considerably increased the number of cells undergoing apoptosis, resulting in a dose-dependent inhibition of cancer cell growth, which was associated with a much better effect on up-regulation of the expression of BCL2-associated X protein (Bax), caspase 9, etc. More importantly, treatment with Ta1-iRGD was more efficacious than treatment with Ta1 in vivo. This study highlights the importance of iRGD on enhancement of cell penetration and tumor accumulation. In summary, our findings demonstrate that the novel modified Tα1 developed in this study has the potential to be used for treating breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects

Lao

et al. 2015

Apoptosis

View full text Add to dashboard Cite

show abstract

“…The underlying mechanism of action of these compounds is thought to be an increase of proinflammatory cytokines, T cell proliferation and differentiation as well as antigen expression on tumor cells resulting in the induction of a tumor-specific cytotoxicity [19,20]. Indeed, preliminary phase II trials of thymostimulin in patients with HCC were notable for their tumor response rate and the occurrence of complete responses, resulting in a median overall survival of up to 11.5 months [11,12].…”

Section: Discussionmentioning

confidence: 99%

Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

et al. 2010

View full text Add to dashboard Cite

BackgroundThymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial.MethodsThe study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky ≥60%/Child-Pugh ≤ 12) were randomised to receive thymostimulin 75 mg s.c. 5×/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol.ResultsTwelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure.ConclusionsIn our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation.Trial RegistrationCurrent Controlled Trials ISRCTN64487365.

show abstract

“…Moody et al investigated the effects of T␣1 on mammary carcinogenesis in fisher rats and found that T␣1 could reduce mammary carcinoma incidence and prolong survival time [52]. In another breast adenoma model, T␣1 increased the survival time in female C3(1)SV40T antigen transgenic mice and fisher rats, but it remained to be determined whether the immune response also increased or not [53]. The antitumor activity of T␣1 was most effective when the lung adenomas were small, which was based on studies proformed by Moody who gave T␣1 daily to A/J mice bearing lung adenoma [53].…”

Section: Antitumormentioning

confidence: 99%

Thymosin alpha 1: Biological activities, applications and genetic engineering production

Liu

Wang

2010

Peptides

View full text Add to dashboard Cite

Thymosin alpha 1 (Tα1), a 28-amino acid peptide, was first described and characterized from calf thymuses in 1977. This peptide can enhance T-cell, dendritic cell (DC) and antibody responses, modulate cytokines and chemokines production and block steroid-induced apoptosis of thymocytes. Due to its pleiotropic biological activities, Tα1 has gained increasing interest in recent years and has been used for the treatment of various diseases in clinic. Accordingly, there is an increasing need for the production of this peptide. So far, Tα1 used in clinic is synthesized using solid phase peptide synthesis. Here, we summarize the genetic engineering methods to produce Tα1 using prokaryotic or eukaryotic expression systems. The effectiveness of these biological products in increasing the secretion of cytokines and in promoting lymphocyte proliferation were investigated in vitro studies. This opens the possibility for biotechnological production of Tα1 for the research and clinical applications.

show abstract

Thymosin α1 as a Chemopreventive Agent in Lung and Breast Cancer

Cited by 30 publications

References 24 publications

A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects

A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects

Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

Thymosin alpha 1: Biological activities, applications and genetic engineering production

Contact Info

Product

Resources

About