Modulating Effects of the Synthetic Thymic Dipeptide Pidotimod on the Immune System in the Aging Rat

Chiarenza, Annalisa; Iurato, Maria Pierangela; Barbera, Nunziata; Lempereur, Laurence; Cantarella, Giuseppina; Scapagnini, U.; Bernardini, Renato

doi:10.1111/j.1600-0773.1994.tb01109.x

Cited by 9 publications

(11 citation statements)

References 12 publications

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“…In addition, our data suggest that NGF could be used as a marker of breast cancer cells. The prognostic value of both p75 NTR and TrkA receptors (Descamps et al, 2001b) as well as the possibility of targeting p140 TrkAmediated mitogenic signaling with tamoxifen, a drug commonly used in breast cancer therapy, has already been reported (Chiarenza et al, 2001). Immunohistochemistry analysis of NGF in tumor biopsies revealed differences of intensity in the carcinomas studied.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated that nerve growth factor (NGF), the first discovered neurotrophic factor, is also a potent activator of both the survival and proliferation of breast cancer cells (Descamps et al, 1998(Descamps et al, , 2001a). In addition, the level of NGF receptor expression has some prognostic value (Descamps et al, 2001b) and the antiestrogen drug tamoxifen, which is widely used in breast cancer therapy, is able to inhibit the mitogenic effect of this neurotrophin in breast cancer cells (Chiarenza et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Nerve growth factor overexpression and autocrine loop in breast cancer cells

et al. 2003

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We show here that nerve growth factor (NGF), the canonical neurotrophic factor, is synthesized and released by breast cancer cells. High levels of NGF transcript and protein were detected in breast cancer cells by reverse transcription-PCR, Western blotting, ELISA assay and immunohistochemistry. Conversely, NGF production could not be detected in normal breast epithelial cells at either the transcriptional or protein level. Confocal analysis indicated the presence of NGF within classical secretion vesicles. Breast cancer cell-produced NGF was biologically active, as demonstrated by its ability to induce the neuronal differentiation of embryonic neural precursor cells. Importantly, the constitutive growth of breast cancer cells was strongly inhibited by either NGF-neutralizing antibodies or K-252a, a pharmacological inhibitor of NGF receptor TrkA, indicating the existence of an NGF autocrine loop. Together, our data demonstrate the physiological relevance of NGF in breast cancer and its potential interest as a marker and therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nerve growth factor overexpression and autocrine loop in breast cancer cells

et al. 2003

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“…The trophic function of NGF for breast cancer cells, involving both mitogenic and antiapoptotic activities, has recently been shown (8,12). The prognostic value of both p75 NTR and TrkA receptors has also secondarily been reported (26), as has the possibility of targeting p140 TrkA -mediated mitogenic signaling with tamoxifen, a drug commonly used in breast cancer therapy (27). Our present data also suggest that targeting the p75 NTR /TRADD/NF-B signaling pathway may be a promising avenue for future treatment of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor Receptor-associated Death Domain Protein Is Involved in the Neurotrophin Receptor-mediated Antiapoptotic Activity of Nerve Growth Factor in Breast Cancer Cells

Yazidi‐Belkoura¹,

Adriaenssens²,

Dollé³

et al. 2003

Journal of Biological Chemistry

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The common neurotrophin receptor p75NTR has been shown to initiate intracellular signaling that leads either to cell survival or to apoptosis depending on the cell type examined; however, the mechanism by which p75 NTR initiates its intracellular transduction remains unclear. We show here that the tumor necrosis factor receptor-associated death domain protein (TRADD) interacts with p75 NTR upon nerve growth factor (NGF) stimulation. TRADD could be immunodetected after p75NTR immunoprecipitation from MCF-7 breast cancer cells stimulated by nerve growth factor. In addition, confocal microscopy indicated that NGF stimulation induced the plasma membrane localization of TRADD. Using a dominant negative form of TRADD, we also show that interactions between p75 NTR and TRADD are dependent on the death domain of TRADD, thus demonstrating its requirement for binding. Furthermore, the p75 NTR -mediated activation of NF-B was inhibited by transfection with a dominant negative TRADD, resulting in an inhibition of NGF antiapoptotic activity. These results thus demonstrate that TRADD is involved in the p75 NTR -mediated antiapoptotic activity of NGF in breast cancer cells.

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“…Mitogen-induced IL-2 secretion was also significantly greater in lymphocyte cultures from treated aged rats, but not in untreated 2 month-old rats. Moreover, the weight of the thymus resulted significantly higher both in young and old rats exposed to pidotimod than in controls (7)(8). In vitro stimulating activity of pidotimod on peripheral.…”

Section: Animal Studiesmentioning

confidence: 99%

“…Chiarenza et al investigated the ex vivo effects of pidotimod on PBMC immune functions in ageing rats (24 months) compared to younger (2 months) and placebo treated animals (7)(8). Young and ageing rats underwent i.p.…”

Section: Animal Studiesmentioning

confidence: 99%

Pidotimod: A Reappraisal

Riboldi

Gerosa

Meroni

2009

Int J Immunopathol Pharmacol

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Pidotimod (Polimod ®) is a synthetic dipeptide molecule with biological and immunological activity on both the adaptive and the innate immune responses. In vitro studies, both from animal and human specimens, have documented a good activity on innate and adaptive immune responses and have been confirmed by in vivo studies. These activities have been applied in clinical studies demonstrating the efficacy of pidotimod in reducing the rate of recurrent infections of the upper respiratory and urinary tracts in children. The same results were obtained in recurrent respiratory tract infections in adults. Interestingly, these effects are more evident in the setting of immune defects such as senescence, Down's syndrome, and cancer.Pidotimod (Polimod ®) is a synthetic dipeptide molecule with biological and immunological activity on both the adaptive and the innate immune responses (Fig. 1). In comparison with biological response modifiers of extractive origin, the synthetic process ensures a high purity product with a high reproducibility among batches. Pidotimod is rapidly absorbed by the gastrointestinal tract with a bioavailability of 45%. The plasma half life is 4 h with poor metabolism and renal elimination of the unmodified molecule.In vitro studies from both animal and human specimens have documented a good activity on innate and adaptive immune responses and have been confirmed by in vivo studies. These activities have been applied in clinical studies demonstrating the efficacy of pidotimod in reducing the rate of recurrent infections of the upper respiratory and urinary tract in children. The same results were obtained in recurrent respiratory tract infections in adults. More importantly, these effects are more evident in the setting of immune defects such as senescence, Down's syndrome, and cancer. The aim of this review is to analyze the effects of pidotimod on the innate and adaptive immunity and the studies of clinical efficacy. Animal studiesThe first experiments were designed to demonstrate a protective effect of pidotimod in experimental infections in mice. Mice injected intraperitoneally (i.p.) with P. mirabilis, P. vulgaris, S. aureus, K. pneumoniae or P. aeruginosa are protected from death when treated concomitantly with repeated injections ofpidotimod. The protective effect reached a 100% survival with Proteus strains, 90% with S. aureus and 40% with more aggressive bacteria such as Pseudomonas and Klebsiella strains. This effect is dose-dependent and can be strengthened by a synergistic activity with beta-lactam antibiotics

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Modulating Effects of the Synthetic Thymic Dipeptide Pidotimod on the Immune System in the Aging Rat

Cited by 9 publications

References 12 publications

Nerve growth factor overexpression and autocrine loop in breast cancer cells

Nerve growth factor overexpression and autocrine loop in breast cancer cells

Tumor Necrosis Factor Receptor-associated Death Domain Protein Is Involved in the Neurotrophin Receptor-mediated Antiapoptotic Activity of Nerve Growth Factor in Breast Cancer Cells

Pidotimod: A Reappraisal

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