tretinoin and Remission--Spontaneous

In a multi-centre study 291 patients with psoriasis were treated with (a) oral doses of the recently developed retinoid Ro 10-9359, (b) classical local dithranol application, and (c) both. In a preliminary evaluation of 203 patients treated orally excellent or good results were obtained in 120 (61%), no response in 31 (15.8%). The initial dose was 1.0 mg/kg body-weight daily, i.e. 50-75 mg, which was then reduced to 25-50 mg daily. A clinical response was noted after 2-3 weeks. Particularly, severe erythrodermic and pustular forms of the disease responded surprisingly well to the drug so that cytostatic agents were avoided. Under long-term administration, however, relapses were still seen. Most side-effects were reasonably well tolerated. But in 14% of patients the drug had to be discontinued because of hair loss, paronychia or slight elevation of transaminases (up to 40 U/I). This new drug is thus a potent antipsoriatic agent: it is effective, easily controlled and causes only moderate side-effects.

Topics: Administration, Oral; Adolescent; Adult; Anthralin; Child; Female; Humans; Male; Middle Aged; Psoriasis; Recurrence; Remission, Spontaneous; Time Factors; Tretinoin; Vitamin A

Topics: Aged; Arsenic Trioxide; Biopsy, Needle; Drug Eruptions; Follow-Up Studies; Humans; Immunohistochemistry; Leukemia, Promyelocytic, Acute; Male; Remission, Spontaneous; Risk Assessment; Treatment Outcome; Tretinoin

Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4(+) T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance.

Topics: Agranulocytosis; Amodiaquine; Animals; Cells, Cultured; Chemical and Drug Induced Liver Injury; Cyclosporine; Cytokines; Disease Models, Animal; Humans; Killer Cells, Natural; Male; Mice; Mice, Inbred C57BL; Rats; Rats, Inbred BN; Remission, Spontaneous; Spinocerebellar Degenerations; T-Lymphocytes, Regulatory; Th17 Cells; Tretinoin

A fundamental goal in cancer biology is to identify the cells and signalling pathways that are keys to induce tumour regression. Here we use a spontaneously self-regressing tumour, cutaneous keratoacanthoma (KAs), to identify physiological mechanisms that drive tumour regression. By using a mouse model system that recapitulates the behaviour of human KAs, we show that self-regressing tumours shift their balance to a differentiation programme during regression. Furthermore, we demonstrate that developmental programs utilized for skin hair follicle regeneration, such as Wnt, are hijacked to sustain tumour growth and that the retinoic acid (RA) signalling pathway promotes tumour regression by inhibiting Wnt signalling. Finally, we find that RA signalling can induce regression of malignant tumours that do not normally spontaneously regress, such as squamous cell carcinomas. These findings provide new insights into the physiological mechanisms of tumour regression and suggest therapeutic strategies to induce tumour regression.

Topics: Animals; Carcinoma, Squamous Cell; Disease Models, Animal; Hair Follicle; Keratoacanthoma; Mice; Remission, Spontaneous; Skin Neoplasms; Stem Cells; Tretinoin; Wnt Signaling Pathway

Topics: Adolescent; Adult; Child; Humans; Molluscum Contagiosum; Molluscum contagiosum virus; Remission, Spontaneous; Tretinoin

Fourteen patients with treatment-resistant cystic and conglobate acne were treated for four months with oral 13-cis-retinoic acid, a synthetic isomer of naturally occurring all-trans-retinoic acid. The average dose was 2.0 mg per kilogram per day. Thirteen patients experienced complete clearing of their disease; the other had 75 per cent improvement, as determined by the number of acne nodules and cysts present before and after therapy. Prolonged remissions, currently lasting as long as 20 months after discontinuation of therapy, have been observed in all 14 patients. Clinical toxicity was limited to the skin and mucous membranes in most patients and was dose dependent and rapidly reversible upon discontinuation of therapy. The mechanism of action of 13-cis-retinoic acid in the therapy of acne probably involves a direct inhibitory effect of the drug on the sebaceous gland.

Topics: Acne Vulgaris; Adolescent; Adult; Female; Humans; Isomerism; Lipids; Male; Remission, Spontaneous; Sebum; Time Factors; Tretinoin; Vitamin A

Topics: Adult; Furocoumarins; Humans; Male; Middle Aged; Photochemotherapy; Psoriasis; Remission, Spontaneous; Tretinoin; Vitamin A