Cromolyn Sodium: Fitting an Old Friend into Current Asthma Treatment

Storms, William W.; Kaliner, Michael

doi:10.1081/jas-200052017

Cited by 8 publications

(11 citation statements)

References 51 publications

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“…Originally, Cromolyn was developed as an anti-inflammatory drug used for prophylactic treatment of bronchial asthma and allergic rhinitis. 29 In addition, it has been reported that Cromolyn binds specifically to other members of the S100 protein family (S100A1, S100A12 and S100A13). 30, 31 Recently, Cromolyn has been shown to block the interaction with RAGE, and to inhibit tumor growth.…”

Section: Discussionmentioning

confidence: 99%

S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer

et al. 2014

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Despite progresses in diagnosis and treatment, pancreatic cancer continues to have the worst prognosis of all solid malignant tumors. Recent evidences suggest that the metastasis-promoting protein S100P stimulates pancreatic tumor proliferation, survival, invasion and metastasis progression through extracellular functions. Moreover, its expression is strongly correlated with poor prognosis in patients with several types of cancer although the entire molecular mechanism responsible for the diverse biological functions is not fully understood. We showed that extracellular S100P stimulates pancreatic carcinoma BxPC3 cell line by promoting cell proliferation. We also demonstrated that S100P induces, in this cell line, the phosphorylation of IκBα and the secretion of matrix metalloproteinase 9 (MMP-9). In addition, treatment with S100P protected cells from injuries induced by the cytotoxic agent Gemcitabine. On the basis of these results, we developed function-blocking anti-S100P monoclonal antibodies (mAbs) that abolished all of its in vitro activities. Furthermore, in vivo treatment with the candidate 2H8 antibody decreased tumor growth and liver metastasis formation in a subcutaneous and orthotopic BxPC3 tumor model. We conclude here that a therapeutic strategy blocking the extracellular activity of S100P by means of specific mAbs could be an attractive therapeutic approach as a single agent or in combination with target-directed or chemotherapeutic drugs to treat pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer

et al. 2014

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“…12–15 For this reason, cromolyn is often characterized clinically as a “mast cell stabilizer”, 16 and this drug is now used for the treatment of other diseases thought to involve mast cell activation, including allergic rhinitis, allergic conjunctivitis, and mastocytosis. 17 …”

mentioning

confidence: 99%

Evidence questioning cromolyn's effectiveness and selectivity as a ‘mast cell stabilizer' in mice

Oka

Kalesnikoff

Starkl

et al. 2012

Laboratory Investigation

120

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Cromolyn, widely characterized as a “mast cell stabilizer”, has been used in mice to investigate the biological roles of mast cells in vivo. However, it is not clear to what extent cromolyn can either limit the function of mouse mast cells or influence biological processes in mice independently of effects on mast cells. We confirmed that cromolyn (at 10 mg/kg in vivo or 10 – 100 μM in vitro) can inhibit IgE-dependent mast cell activation in rats in vivo (measuring Evans blue extravasation in passive cutaneous anaphylaxis and increases in plasma histamine in passive systemic anaphylaxis) and in vitro (measuring peritoneal mast cell β-hexosaminidase release and prostaglandin D2 synthesis). However, under the conditions tested, cromolyn did not inhibit those mast cell-dependent responses in mice. In mice, cromolyn also failed to inhibit the ear swelling or leukocyte infiltration at sites of passive cutaneous anaphylaxis. Nor did cromolyn inhibit IgE-independent degranulation of mouse peritoneal mast cells induced by various stimulators in vitro. At 100 mg/kg, a concentration ten times higher than that which inhibited passive systemic anaphylaxis in rats, cromolyn significantly inhibited the increases in plasma concentrations of mouse mast cell protease-1 (but not of histamine) during passive systemic anaphylaxis, but had no effect on the reduction in body temperature in this setting. Moreover, this concentration of cromolyn (100 mg/kg) also inhibited LPS-induced TNF production in genetically mast cell-deficient C57BL/6-KitW-sh/W-sh mice in vivo. These results question cromolyn’s effectiveness and selectivity as an inhibitor of mast cell activation and mediator release in the mouse.

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“…Considering that all these pharmacological agents are not MC specific being active also on other cell types [81,82], no direct conclusions could be drawn on the role of MCs in EAE by these pharmacological studies.…”

Section: Mast Cells In Cns Autoimmunitymentioning

confidence: 99%

Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Costanza¹,

Colombo

Pedotti³

2012

IJMS

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Mast cells (MCs) are best known as key immune players in immunoglobulin E (IgE)-dependent allergic reactions. In recent years, several lines of evidence have suggested that MCs might play an important role in several pathological conditions, including autoimmune disorders such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Since their first description in MS plaques in the late 1800s, much effort has been put into elucidating the contribution of MCs to the development of central nervous system (CNS) autoimmunity. Mouse models of MC-deficiency have provided a valuable experimental tool for dissecting MC involvement in MS and EAE. However, to date there is still major controversy concerning the function of MCs in these diseases. Indeed, although MCs have been classically proposed as having a detrimental and pro-inflammatory role, recent literature has questioned and resized the contribution of MCs to the pathology of MS and EAE. In this review, we will present the main evidence obtained in MS and EAE on this topic, and discuss the critical and controversial aspects of such evidence.

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Cromolyn Sodium: Fitting an Old Friend into Current Asthma Treatment

Cited by 8 publications

References 51 publications

S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer

S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer

Evidence questioning cromolyn's effectiveness and selectivity as a ‘mast cell stabilizer' in mice

Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

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