Effect of tibolone on the survival of early stage cervical adenocarcinoma patients.

OBJECTIVE: Gynecologic oncologists are uncertain about the safety of tibolone application in cervical adenocarcinoma (AC) patients. This study examined the possible adverse effects of tibolone on the survival of cervical AC patients. METHODS: Medical records of 70 cervical AC patients with International Federation of Gynecology and Obstetrics stages IA to IB were reviewed. A bilateral salpingo-oophorectomy was performed in all patients, and survival outcomes between tibolone users (n=38) and non-users (n=32) were compared. RESULTS: A comparison of the tibolone users with non-users revealed similar clinicopathological variables. Progression-free survival (P=0.34) and overall survival (P=0.22) were similar in the users and non-users. The risks of progression (hazard ratio [HR], 1.71; 95% confidence interval [CI], 0.46-6.37; P=0.43) and death (HR, 1.59; 95% CI, 0.06-45.66; P=0.79) were also similar in both groups. CONCLUSION: Tibolone has no adverse effect on the survival of cervical AC patients and can be administered safely to this population. These findings may be helpful in improving the quality of life of cervical AC patients.

In vitro derby imaging of cancer biomarkers using quantum dots.

Semiconductor quantum dots (QDs), which have broad absorption with narrow emission spectra, are useful for multiplex imaging. Here, fluorescence derby imaging using dual color QDs conjugated by the AS1411 aptamer (targeting nucleolin) and the arginine-glycine-aspartic acid (targeting the integrin alpha(v)beta(3)) in cancer cells is reported. Simultaneous fluorescence imaging of cellular distribution of nucleolin and integrin alpha(v)beta(3) using QDs enables easy monitoring of separate targets in the cancer cells and the normal healthy cells. These results suggest the feasibility of a concurrent visualization of QD-based multiple cancer biomarkers using small molecules such as aptamer or peptide ligands.

Bioimaging of geographically adjacent proteins in a single cell by quantum dot-based fluorescent resonance energy transfer.

Thousands of proteins are simultaneously involved in the maintenance of a single cancer cell. Fluorescent resonance energy transfer (FRET) is one of the most general techniques for imaging biologically interacting molecules in a cell. Here, we applied FRET to image the co-localization of two proteins that do not interact biologically (nucleolin and integrin α(v) ß(3),) both of which are highly expressed in the plasma membrane of cancer cells. AS1411 aptamer, which targets nucleolin, was labeled by Cy3 (Cy3-AS1411) and arginine-glycine-aspartic acid (RGD) peptide, which targets integrin α(v) ß(3) , was conjugated with quantum dot (525 nm, Qd) Qd arginine-glycine-aspartic acid (Qd-RGD). FRET activities between Cy3-AS1411 and Qd-RGD were measured in HeLa cells, a human cervical cancer cell line. FRET phenomena between Qd and Cy3 showed good compatibility according to proximity. The fluorescence signature using Qd-RGD and Cy3-AS1411 showed that nucleolin and integrin α(v) ß(3) proteins were highly expressed in HeLa cells. Co-incubation of Qd-RGD and Cy3-AS1411 in a single HeLa cell demonstrated that the fluorescence overlay by FRET was quantitatively and geographically quite different from that of individual confocal images. These results suggest that Qd-based FRET analysis can provide information on geographical co-localization of proteins in naïve cells, which is very important for determining the molecular and cellular functions of genes involved in cancers and other clinical diseases.

Bioimaging of the unbalanced expression of microRNA9 and microRNA9* during the neuronal differentiation of P19 cells.

Generally, the 3'-end of the duplex microRNA (miR) precursor (pre-miR) is known to be stable in vivo and serve as a mature form of miR. However, both the 3'-end (miR9) and 5'-end (miR9*) of a brain-specific miR9 have been shown to function biologically in brain development. In this study, real-time PCR analysis and in vitro/in vivo bioluminescent imaging demonstrated that the upstream region of a primary miR9-1 (pri-miR9-1) can be used to monitor the highly expressed pattern of endogenous pri-miR9-1 during neurogenesis, and that the Luciferase reporter gene can image the unequal expression patterns of miR9 and miR9* seen during the neuronal differentiation of P19 cells. This demonstrates that our bioimaging system can be used to study the participation of miRs in the regulation of neuronal differentiation.