Binary combination effects of some pharmacologically active chemicals as promoters of tumorigenesis

Rao, Venkateswara

doi:10.1002/jps.2600810502

Cited by 6 publications

(1 citation statement)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, it has been demonstrated that some antiallergic compounds, such as astemizole and hydroxyzine, have the propensity to stimulate cancer growth in mice [10]; it is known that as a class, drugs that promote cancer growth tend to be immunosuppressive rather than determine tumor cell proliferation [11]. Along this line, this study also investigates the effects of mizolastine on parameters which reflect the immune response efficacy.…”

Section: Introductionmentioning

confidence: 99%

Effects of Mizolastine in vitro on Human Immunocompetent and Airway Cells: Evidence for Safety and Additional Property

Oddera

Cagnoni

Dellacasa

et al. 2000

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: Mizolastine is a potent, peripherally acting, selective H1-receptor antagonist with potential anti-inflammatory properties. The aim of the study was to evaluate the in vitro effects of mizolastine on the expression of adhesion molecules by primary human airway epithelial and stromal cultures; moreover, the activity of mizolastine on parameters which reflect the immune response efficacy was investigated. Methods: Airway epithelial and stromal cells were collected from hypereosinophilic subjects by enzymatic digestion of polyps or turbinates. Cells were stimulated with interferon (IFN)-γ (500 IU/ml) in the presence of various mizolastine concentrations (6 × 10^–8–6 × 10^–6 M) for 24 h and the expression of CD106, CD54, CD58 and HLA class I was evaluated. Peripheral blood mononuclear cells from healthy volunteers were incubated with 1% phytohemagglutinin or anti-CD3 monoclonal antibody (20 ng/ml) in the presence of mizolastine, then T lymphocyte proliferation, HLA-DR expression and T cell subpopulations were evaluated. Results: Both in epithelial and stromal cultures, IFN-γ significantly upregulated all of the tested surface molecules (p < 0.05). The highest dose of mizolastine (6 × 10^–6 M), corresponding to 10-fold the peak plasma level after a single oral administration of 10 mg, was able to act on fibroblasts, significantly downregulating the expression of CD54 (p < 0.05). Regarding T lymphocyte proliferation, the addition of mizolastine did not induce any significant change; furthermore, mizolastine was ineffective at all of the tested concentrations on both HLA-DR expression and CD4+/CD8+ ratio. Conclusions: This study demonstrated that mizolastine is able to selectively downregulate CD54 expression on stimulated stromal but not epithelial cells without impairing the immune system effectors. The possible clinical significance of these results are an antiallergic property and CD54 modulation on fibroblasts with a good safety profile as far as the lymphocyte response is concerned.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of Mizolastine in vitro on Human Immunocompetent and Airway Cells: Evidence for Safety and Additional Property

Oddera

Cagnoni

Dellacasa

et al. 2000

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

Antidepressant Therapy

Cm²

1995

Arch Dermatol

View full text Add to dashboard Cite

Enhancement of tumor growth by drugs with some common molecular actions

LaBella

Brandes

1996

Mol. Carcinog.

View full text Add to dashboard Cite

A group of structurally related drugs representing diverse therapeutic classes share, among a number of pharmacological properties, enhancement of tumor growth in several rodent models of malignancy. One common action, the inhibition of histamine binding to and catalytic activity of cytochrome P450 monooxygenases, is highly correlated with potency to enhance tumor growth. Among members of this drug ensemble, the antiestrogen tamoxifen has been shown in controlled clinical studies to increase the incidence of uterine and gastrointestinal cancer and to accelerate the course of gastric cancer, and the tamoxifen analogue clomiphene has been linked to neuroblastoma and the tricyclic group of antidepressants to ovarian cancer. The determination of drug affinities for protein modulators of cell growth, proliferation, and transformation suggests a strategy for identifying at least some classes of chemicals that impart oncologic risks to humans.

show abstract

Binary combination effects of some pharmacologically active chemicals as promoters of tumorigenesis

Cited by 6 publications

References 23 publications

Effects of Mizolastine in vitro on Human Immunocompetent and Airway Cells: Evidence for Safety and Additional Property

Effects of Mizolastine in vitro on Human Immunocompetent and Airway Cells: Evidence for Safety and Additional Property

Antidepressant Therapy

Enhancement of tumor growth by drugs with some common molecular actions

Contact Info

Product

Resources

About