Selective overexpression of Human epididymal secretory protein E4 (HE4) points to a role in ovarian cancer tumorigenesis but little is known about the role the HE4 gene or the gene product plays. Here we show that elevated HE4 serum levels correlate with chemoresistance and decreased survival rates in EOC patients. HE4 overexpression promoted xenograft tumor growth and chemoresistance against cisplatin in an animal model resulting in reduced survival rates. HE4 displayed responses to tumor microenvironment constituents and presented increased expression as well as nuclear translocation upon EGF, VEGF and Insulin treatment and nucleolar localization with Insulin treatment. HE4 interacts with EGFR, IGF1R, and transcription factor HIF1α. Constructs of antisense phosphorothio-oligonucleotides targeting HE4 arrested tumor growth in nude mice. Collectively these findings implicate increased HE4 expression as a molecular factor in ovarian cancer tumorigenesis. Selective targeting directed towards the HE4 protein demonstrates therapeutic benefits for the treatment of ovarian cancer.

Antiestrogens including tamoxifen and fulvestrant have been evaluated as chemotherapeutics for ovarian cancer, particularly in cases of platinum resistant disease. Human epididymis protein 4 (HE4) is highly overexpressed in women with ovarian cancer and overexpression of HE4 has been found to correlate with platinum resistance. However, the role of HE4 in modulating responses to hormones and hormonal therapy has not been characterized in ovarian cancer. Here we demonstrate that 17β-estradiol, tamoxifen, and fulvestrant induce nuclear and nucleolar translocation of HE4 and that HE4 overexpression induces resistance to antiestrogens. HE4 was found to interact with estrogen receptor-α (ER-α), and HE4 overexpression resulted in ER-α downregulation in vitro and in human ovarian cancers. We identified a novel role for importin-4 in governing the nuclear transport of HE4. Treatment with ivermectin, an importin inhibitor, blocked HE4/importin-4 nuclear accumulation and sensitized HE4-overexpressing ovarian cancer cells to fulvestrant and tamoxifen.

A sensor node for sampling water and checking for the presence of harmful bacteria such as E. coli in water sources was developed in this research. A chromogenic enzyme substrate assay method was used to easily detect coliform bacteria by monitoring the color change of the sampled water mixed with a reagent. Live webcam image streaming to the web browser of the end user with a Wi-Fi connected sensor node shows the water color changes in real time. The liquid can be manipulated on the web-based user interface, and also can be observed by webcam feeds. Image streaming and web console servers run on an embedded processor with an expansion board. The UART channel of the expansion board is connected to an external Arduino board and a motor driver to control self-priming water pumps to sample the water, mix the reagent, and remove the water sample after the test is completed. The sensor node can repeat water testing until the test reagent is depleted. The authors anticipate that the use of the sensor node developed in this research can decrease the cost and required labor for testing samples in a factory environment and checking the water quality of local water sources in developing countries.