A Case of Advanced Lung Adenocarcinoma Harboring an Epidermal Growth Factor Receptor(EGFR) Exon 20 Insertion, D770_N771insSVD.

A 57-year-old female was diagnosed as having advanced lung adenocarcinoma. Combination chemotherapy using cisplatin plus pemetrexed was introduced. However, her disease progressed during the maintenance therapy with pemetrexed. Subsequent therapies could not control the disease. Later, it was found that her lung cancer harbored an epidermal growth factor receptor(EGFR)exon 20 insertion, D770_N771insSVD. Afatinib, a second-generation EGFR-tyrosine kinase inhibitor (TKI), was administered as the fourth-line treatment and reduced the size in several lesions. Although EGFR-TKIs are generally not recommended as the first-line treatment for lung cancers with EGFR exon 20 insertions, afatinib could be a useful therapeutic option in the second-line or later therapy for this type of exon 20 insertion, D770_N771insSVD.

Effect of the expression of aquaporins 1 and 3 in mouse oocytes and compacted eight-cell embryos on the nucleation temperature for intracellular ice formation.

The occurrence of intracellular ice formation (IIF) is the most important factor determining whether cells survive a cryopreservation procedure. What is not clear is the mechanism or route by which an external ice crystal can traverse the plasma membrane and cause the heterogeneous nucleation of the supercooled solution within the cell. We have hypothesized that one route is through preexisting pores in aquaporin (AQP) proteins that span the plasma membranes of many cell types. Since the plasma membrane of mature mouse oocytes expresses little AQP, we compared the ice nucleation temperature of native oocytes with that of oocytes induced to express AQP1 and AQP3. The oocytes were suspended in 1.0  M ethylene glycol in PBS for 15  min, cooled in a Linkam cryostage to -7.0  ° C, induced to freeze externally, and finally cooled at 20  ° C/min to -70  ° C. IIF that occurred during the 20  ° C/min cooling is manifested by abrupt black flashing. The mean IIF temperatures for native oocytes, for oocytes sham injected with water, for oocytes expressing AQP1, and for those expressing AQP3 were -34, -40, -35, and -25  ° C respectively. The fact that the ice nucleation temperature of oocytes expressing AQP3 was 10-15  ° C higher than the others is consistent with our hypothesis. AQP3 pores can supposedly be closed by low pH or by treatment with double-stranded Aqp3 RNA. However, when morulae were subjected to such treatments, the IIF temperature still remained high. A possible explanation is suggested.