Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing.

PURPOSE: We sought to determine the mechanisms of downregulation of the airway transcription factor Foxa2 in lung cancer and the expression status of Foxa2 in non-small-cell lung cancer (NSCLC). METHODS: A series of 25 lung cancer cell lines were evaluated for Foxa2 protein expression, FOXA2 mRNA levels, FOXA2 mutations, FOXA2 copy number changes and for evidence of FOXA2 promoter hypermethylation. In addition, 32 NSCLCs were sequenced for FOXA2 mutations and 173 primary NSCLC tumors evaluated for Foxa2 expression using an immunohistochemical assay. RESULTS: Out of the 25 cell lines, 13 (52%) had undetectable FOXA2 mRNA. The expression of FOXA2 mRNA and Foxa2 protein were congruent in 19/22 cells (p = 0.001). FOXA2 mutations were not identified in primary NSCLCs and were infrequent in cell lines. Focal or broad chromosomal deletions involving FOXA2 were not present. The promoter region of FOXA2 had evidence of hypermethylation, with an inverse correlation between FOXA2 mRNA expression and presence of CpG dinucleotide methylation (p < 0.0001). In primary NSCLC tumor specimens, there was a high frequency of either absence (42/173, 24.2%) or no/low expression (96/173, 55.4%) of Foxa2. In 130 patients with stage I NSCLC there was a trend towards decreased survival in tumors with no/low expression of Foxa2 (HR of 1.6, 95%CI 0.9-3.1; p = 0.122). CONCLUSIONS: Loss of expression of Foxa2 is frequent in lung cancer cell lines and NSCLCs. The main mechanism of downregulation of Foxa2 is epigenetic silencing through promoter hypermethylation. Further elucidation of the involvement of Foxa2 and other airway transcription factors in the pathogenesis of lung cancer may identify novel therapeutic targets.

Occurrence and distribution of larval lanternfish (Myctophidae) from the southwest Atlantic Ocean

This study analyzes the occurrence and distribution of lanternfish (Myctophidae) larvae along the Brazilian coast (12-22ºS) between 200 m and the surface. Three cruises were conducted during the spring/1998, winter/1999 and autumn/2000. A total of 3,394 lanternfish larvae were identified representing 27 species and Lepidophanes guentheri (Goode & Bean, 1896) was the most abundant. Most of the identified taxa were in the postflexion stage. Myctophid larvae were more numerous during the winter. Most taxa were distributed widely from 12-22ºS, including some seamounts, and occurred mainly outside the 1,000 m isobath. Although there was no difference in the myctophid community among the coastal, oceanic and seamount regions it was significantly different during the three seasons. During the spring and autumn Hygophum reinhardtii (Lütken, 1892) was the discriminating species while in the winter there were more L. guentheri.

Occurrence and distribution of larval lanternfish (Myctophidae) from the southwest Atlantic Ocean

This study analyzes the occurrence and distribution of lanternfish (Myctophidae) larvae along the Brazilian coast (12-22ºS) between 200 m and the surface. Three cruises were conducted during the spring/1998, winter/1999 and autumn/2000. A total of 3,394 lanternfish larvae were identified representing 27 species and Lepidophanes guentheri (Goode & Bean, 1896) was the most abundant. Most of the identified taxa were in the postflexion stage. Myctophid larvae were more numerous during the winter. Most taxa were distributed widely from 12-22ºS, including some seamounts, and occurred mainly outside the 1,000 m isobath. Although there was no difference in the myctophid community among the coastal, oceanic and seamount regions it was significantly different during the three seasons. During the spring and autumn Hygophum reinhardtii (Lütken, 1892) was the discriminating species while in the winter there were more L. guentheri.

Occurrence and distribution of larval lanternfish (Myctophidae) from the southwest Atlantic Ocean

This study analyzes the occurrence and distribution of lanternfish (Myctophidae) larvae along the Brazilian coast (12-22ºS) between 200 m and the surface. Three cruises were conducted during the spring/1998, winter/1999 and autumn/2000. A total of 3,394 lanternfish larvae were identified representing 27 species and Lepidophanes guentheri (Goode & Bean, 1896) was the most abundant. Most of the identified taxa were in the postflexion stage. Myctophid larvae were more numerous during the winter. Most taxa were distributed widely from 12-22ºS, including some seamounts, and occurred mainly outside the 1,000 m isobath. Although there was no difference in the myctophid community among the coastal, oceanic and seamount regions it was significantly different during the three seasons. During the spring and autumn Hygophum reinhardtii (Lütken, 1892) was the discriminating species while in the winter there were more L. guentheri.

Unsuspected ocular leprosy

Ophtalmic findings suggestive of leprosy include loss of eyebrows and eyelashes, beaded corneal nerves, puntacte subepithelial superior limbal corneal opacities, entropion of the upper eyelids, conjunctival hyperemia an the other canthal area, iris pearls and unexplained unilateral or bilateral 7th nerve histories were presented. The average time interval between the initial presenting complaint the establishment of the correct diagnosis was six years. There is no accurate method of determining the real incidence of leprosy in the United States, but it would appear to be higher than suspected. Ophthalmologists should consider leprosy when examining patients with any of the findings just mentioned, particularly if the patient has a sssociated skin or neurologic findings or nasal stuffiness.