Black porgy, Acanthopagrus schlegeli Bleeker, is a marine protandrous hermaphrodite fish. A Dmrt1 cDNA was cloned and characterized and in order to study the process of sex change in this species, mRNA transcripts of Dmrt1 were monitored. Dmrt1 was specifically transcribed in testis and seminal vesicle in 2-year-old black porgy according to RT-PCR and Southern analysis. A real-time quantification PCR analysis was further developed for the measurement of Dmrt1 transcripts. Dmrt1 transcripts were at significantly higher levels in bisexual testis than bisexual ovary in 1+ and 2+ year-old fish. Dmrt1 transcripts decreased in the functional and bisexual testis of 3-year-old fish. Much higher levels of Dmrt1 transcripts in the bisexual ovary were detected in 1+ year-old fish than in 2+ and 3-year-old fish. No differences in Dmrt1 transcripts were found in bisexual ovaries of 2+ and 3-year-old fish and female ovaries of 3-year-old fish. The data suggest there is relationship of Dmrt1 to the sex change of protandrous black porgy.

Black porgy, Acanthopagrus schlegeli Bleeker, is a marine protandrous hermaphrodite fish. All are functional males at 1-2 yr of age and then become either males or females at 3 yr of age. To study the process of sex change in this species, mRNA transcripts of two estrogen receptors (ERalpha and ERbeta) and an androgen receptor (AR) were monitored. An AR cDNA was cloned and characterized. ERalpha, ERbeta, and AR were differentially transcribed in bisexual testicular and ovarian tissue according to reverse transcription polymerase chain reaction (RT-PCR) and Southern analysis. A real-time quantification PCR analysis was further developed for the measurement of AR, ERalpha, and ERbeta transcripts. ERalpha and AR transcripts were significantly more plentiful in bisexual testis than in bisexual ovary in 1(+)- and 2(+)-yr-old fish. ERalpha, ERbeta, and AR transcripts decreased in the functional testis of 3-yr-old fish. Similar levels of ERbeta and AR were detected in the ovary of sex-changed females and in functional testis of 3-yr-old males. Significantly decreased AR transcripts were found in testicular tissue of bisexual and functional male and female gonads in 3-yr-old fish as compared with 1- and 2-yr-old fish. In contrast, increased ERalpha transcripts were detected in the bisexual ovary and sex-changed ovary of 3-yr-old fish as compared with the bisexual ovary of 1- and 2-yr-old fish. The data suggest a differential sensitivity in the bisexual testicular and ovarian tissue of black porgy.

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The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil ® , the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future.