Purpose: A major obstacle in the treatment of ovarian carcinoma is the intrinsic/acquired resistance to cisplatinbased chemotherapy. Cu-transporting ATPase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed. Our goal was to investigate ATP7B expression in ovarian carcinoma and whether its expression correlates with prognosis and reduced responsiveness to cisplatin treatment.Experimental Design: We retrospectively examined the expression of ATP7B and p53 in primary ovarian carcinoma and its association with chemotherapeutic effect. Tissues were surgically removed from 104 ovarian carcinomas patients who received cisplatin-based chemotherapy. We performed immunohistochemical analysis of ATP7B and p53 using a monoclonal antibody against ATP7B and DO7 antibody against p53 protein in 104 ovarian carcinomas and adjacent nonneoplastic tissues. The significance of ATP7B and p53 in the prognosis of patients with ovarian carcinomas was also examined in the survival analysis of mortality follow-up data covering the period between 1988 and 2001. Furthermore, mutation analysis at the six Cu-binding domain and ATP-binding domain, which may be important for cisplatin transport, were performed using single-strand conformational polymorphism after reverse transcriptase-PCR.Results: A variable degree of cytoplasmic staining of ATP7B in tumor cells was observed in 34.6% (36 of 104 cases) of the analyzed carcinomas. ATP7B expression was not observed in adjacent nonneoplastic tissues. ATP7B positivity in poorly/moderately differentiated carcinoma was significantly higher than that in low malignant potential tumor/well-differentiated carcinoma (P ‫؍‬ 0.0276). Patients with ATP7B-positive tumors had a significantly inferior response to chemotherapy compared with the patients with ATP7B-negative tumors (P ‫؍‬ 0.025). The multivariate Cox regression analysis revealed that ATP7B expression (hazard ratio, 1.8; 95% confidence interval, 1.0 -3.2, P ‫؍‬ 0.048), as well as International Federation of Gynecologists and Obstetricians stage (hazard ratio, 2.0; 95% confidence interval, 1.1-3.6, P ‫؍‬ 0.018), was prognostic for poor disease outcome after adjustment for p53 expression, grade, and residual tumor. p53 expression was detected in 31.5% (26/104 cases). No mutation was observed on the six Cu-binding domain or ATP-binding domain in human ovarian carcinomas expressing ATP7B gene.Conclusions: This study demonstrates that overexpression of ATP7B in ovarian carcinoma is correlated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Therefore, ATP7B expression may be considered as a predictive marker of chemoresistance for cisplatin-based chemotherapy in patients with ovarian carcinoma. We further predict that drugs targeting ATP7B might be useful in combination with cisplatin-based regimen for the improvement of patients with ovarian carcinoma.

Fluorescence and phosphorescence of quinine and its related compounds such as 6-methoxyquinoline are found to exhibit a red shift when excitation is achieved at the long wavelength edge of the first absorption band, and this anomalous shift is investigated in detail. The anomalous shift is observed not only in room temperature fluorescence, but also in low temperature fluorescence and phophorescence. The term edge excitation red shift (EERS) is introduced. After various plausible interpretations we have suggested a logical mechanism for EERS. In the suggested mechanism, EERS is observed if the solvent reorientation relaxation rate is small compared with the emission rate, and the Franck–Condon solvation energy is reasonably large with respect to solvent orientation. All the experimental observations are satisfactorily interpreted within the framework of the suggested mechanism.

No abstract

The edge-excitation red shift previously observed for quinine and related compounds has been shown to exist also for 8-anilinonaphthalene-1-sulfonic acid. The excitation energy dependent spectral shift observed here and the time dependent spectral shift observed by Chakrabarti and Ware have been interpreted satisfactorily in terms of one and the same mechanism. The previously suggested mechanism of the red shift in which the solute–solvent interaction plays an essential role is thus supported. The solvent reorientation relaxation time has been estimated from two different sets of experimental data, one concerned with the excitation energy dependent shift and the other with the time dependent shift. The estimated relaxation times are shown to be entirely different from the dielectric relaxation times of the solvent.

I. IntroductionAMINAR-turbulent transition in hypersonic boundary layers remains a challenging subject. This is especially true of the hypervelocity regime, in which an intriguing phenomenon is the possible damping of second-mode disturbances by chemical and vibrational nonequilibrium processes 1,2 . To generate flows with sufficiently high enthalpy to investigate such effects, the use of shock-tunnel facilities is necessary; furthermore, it is now generally accepted that direct measurements of the instability mechanisms active within the boundary layer, together with a characterization of the free-stream disturbance environment, are required, as simple measurements of transition locations can lead to ambiguous conclusions 3,4 . However, as difficult as the accurate measurement of instability waves in conventional hypersonic facilities can be, in shock tunnels it is appreciably more so. For identical unit Reynolds numbers, the higher stagnation temperature in a shock tunnel means that the dominant second-mode disturbances lie at even higher frequencies (typically hundreds of kHz or higher); moreover, because of the destructive testing environment, hot-wire techniques, a staple for instability measurements in conventional tunnels, cannot be used. Fast-response pressure transducers are an obvious alternative, but recent experiments 5 have highlighted the challenging nature of interpreting data from mechanically-sensitive sensors in the high-noise L