MicroRNA-203 functions as a tumor suppressor in basal cell carcinoma.

Basal cell carcinoma (BCC) of the skin represents the most common malignancy in humans. MicroRNAs (miRNAs), small regulatory RNAs with pleiotropic function, are commonly misregulated in cancer. Here we identify miR-203, a miRNA abundantly and preferentially expressed in skin, to be downregulated in BCCs. We show that activation of the Hedgehog (HH) pathway, critically involved in the pathogenesis of BCCs, as well as the EGFR/MEK/ERK/c-JUN signaling pathway suppresses miR-203. We identify c-JUN, a key effector of the HH pathway, as a novel direct target for miR-203 in vivo. Further supporting the role of miR-203 as a tumor suppressor, in vivo delivery of miR-203 mimics in a BCC mouse model results in the reduction of tumor growth. Our results identify a regulatory circuit involving miR-203 and c-JUN, which provides functional control over basal cell proliferation and differentiation. We propose that miR-203 functions as a 'bona fide' tumor suppressor in BCC, whose suppressed expression contributes to oncogenic transformation via derepression of multiple stemness- and proliferation-related genes, and its overexpression could be of therapeutic value.

Anti-inflammatory activity of beta2-agonists in primary lung epithelial cells is independent of glucocorticoid receptor.

In patients with asthma and chronic obstructive pulmonary disease, the addition of long-acting beta(2)-agonists (LABA) to glucocorticosteroids (GCS) results in better control than increasing the dose of GCS alone. In smooth muscle cells and fibroblasts, one apparent underlying mechanism involves the ability of LABAs to activate the glucocorticoid receptor (GR). The present study investigates the effects of formoterol (FORM), salmeterol (SALM) and budesonide (BUD) on GR activation in bronchial epithelial cells via tumour necrosis factor-alpha-stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) release, GR nuclear translocation and GR-regulated reporter gene activity. Both BUD and FORM inhibited GM-CSF release by < or = 50%. The combination of these two drugs, in clinically relevant concentrations, inhibited GM-CSF release by 85% down to unstimulated levels. A similar inhibition was obtained when combining BUD and SALM. The ability of FORM to inhibit GM-CSF synthesis was not altered by small interfering RNA-mediated depletion of GR and FORM nor SALM-induced GR translocation into the cell nucleus. In addition, FORM did not activate GR-regulated reporter gene activity (SALM was not tested), in contrast to the clear effect of BUD. It was concluded that in bronchial epithelial cells, inhibition of granulocyte-macrophage colony-stimulating factor synthesis by formoterol and salmeterol does not act via previously demonstrated glucocorticoid receptor-related mechanisms, suggesting an alternative pathway in these cells.

[Botulinum toxin. A new therapeutic alternative in spastic dysphonia (laryngeal abductor dystonia)]. / Botulinumtoksin. Et nytt behandlingsalternativ ved spastisk dysfoni (laryngeal adduktordystoni).

Laryngeal dystonia is a condition characterized by involuntary spasms of the laryngeal muscles. In most patients this involves the adductor laryngeal muscles (adductor laryngeal dystonia). Treatment with a variety of therapies, including speech therapy and pharmacotherapy, have led to minimal improvement. Injections of botulinum-toxin (Botox) bilaterally into the vocalis muscles is a new treatment for adductor laryngeal dystonia. Since May 1991 we have treated 23 patients with adductor laryngeal dystonia with botulinum-toxin. In 74% of the patients the voice improved within 24-72 hours, and effect lasted for 2-14 months (average four months). Most of the patients got a breathy voice and a mild sensation of dysphagia during the first week after the injection.

Second malignant neoplasms in patients with head and neck squamous cell carcinomas.

The incidence of second malignant neoplasms (SMN) was analyzed in 714 patients with squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx and larynx. With a minimum follow-up of 3.5 years and 2,540 person-years at risk 84 SMN (10 synchronous and 74 metachronous) developed in 81 patients. The relative risk of SMN was 2.4. The actuarial method showed an annual incidence of SMN of 3.5%. For oral cavity and oropharyngeal tumors the annual incidence of SMN was 4.0% and 3.8% respectively, compared to 2.1% for laryngeal cancer (p < 0.013 and 0.017 respectively). Sex, age or stage of the index tumor did not significantly influence the annual incidence of SMN. After 3 years of follow-up, SMN became more a cause of concern than loco-regional relapse.

[Neck metastases from an unknown primary tumor]. / Metastase til halsen fra ukjent primaertumor.

We evaluate 41 patients treated for cervical lymph node metastases from occult primary carcinomas. Minimum follow-up was two years. 18 patients had metastases from squamous cell carcinoma, 12 from undifferentiated and 11 from adenocarcinoma. The survival rate was best for patients treated with surgery and radiation. The survival rate was 66% for patients with squamous cell and undifferentiated carcinoma, compared with 20% for patients with adenocarcinoma. The survival rate was 85% for patients with N1 and N2A metastases (UICC 1987) from squamous cell and undifferentiated carcinoma, compared with 45% for patients with metastases classified as N2B-N3. The prognosis was better for patients with tumors in the upper 2/3 of the neck than for patients with metastases in the lower 1/3 of the neck. We emphasize the significance of fine-needle aspiration biopsy as a highly accurate, safe and valuable technique in diagnosing malignant tumors of the head and neck.

Morphometric analysis of nasopharyngeal angiofibromas.

Whether recurrences of nasopharyngeal angiofibromas in some way is related to the amount and composition of the vascular components was studied by estimating the volume densities of the vascular lumen, the wall of thin-walled (lined only with endothelial cells) and thick-walled vessels (several cell-layers in the vascular wall) in seven cases of recurring and five non-recurring tumors. The volume density of the vascular compartment was less in recurring compared to non-recurring tumors, 4.3 +/- 2.6% and 8.0 +/- 2.6% respectively (p less than 0.05). The volume density of the wall of thin-walled vessels was 0.7 +/- 0.2% and 1.5 +/- 0.5% for recurring and non-recurring tumors respectively (p less than 0.01). Our findings suggest that nasopharyngeal angiofibromas may be subdivided into two subgroups with different clinical behavior.

Blood parasitemia in a south Texas wintering waterfowl population.

Eleven species of wintering waterfowl were trapped on the Welder Wildlife Foundation, San Patricio County, Texas, between October, 1976 and May, 1977. Blood films were made from 580 ducks. Leucocytozoon simondi, Haemoproteus nettionis, Plasmodium circumflexum, and a microfilaria were found in three species. These blood parasites occurred in 70 lesser scaups (Aythya affinis), 12 blue-winged teals (Anas discors), and 3 ring-necked ducks (Aythya collaris). There was no difference in the rates of infection between the sexes of the three host species. Adult blue-winged teal and lesser scaup were more heavily infected than juveniles. Juvenile ring-necked ducks had more parasites than adults. Blood parasites were found in 85 of 580 ducks (14.6%) throughout the wintering period.