Effect of neoadjuvant chemotherapy on stromal CD10 antigens in breast cancer - a preliminary study.

INTRODUCTION: CD10 is a zinc-dependent peptidase (metalloproteinase). Stromal CD10 expression in breast cancer correlates with poor prognosis, oestrogen receptor negativity and higher grade. CD10 may be a potential target of new cancer therapies as it is involved in cleavage of doxorubicin. AIM: To evaluate the effect of neo-adjuvant anthracycline-based chemotherapy on status of stromal CD10 antigens in breast cancer. MATERIALS AND METHODS: Patients with invasive breast cancer scheduled for anthracycline-based neo-adjuvant chemotherapy were included in the study. Tumor stromal CD10 expression was estimated before and after 3 cycles of chemotherapy, and change in its status was correlated with clinical response to chemotherapy. RESULTS: 16 out of the 29 patients had strong CD10 expression; in these 16 patients, 14 (87.5%) were hormone receptor negative, and 14 (87.5%) had HER-2/neu overexpression. Stromal CD10 expression remained same in 13 out of 29 cases (44.83%) after chemotherapy. There was a change in CD10 expression in the remaining 16 cases (55.17%); in 13 cases (44.83%) it decreased from its pre-chemotherapy status, while its expression increased in 3 cases (10.34%). In cases of complete and partial clinical response, there was no increase in CD10 expression. Where CD10 expression had increased after chemotherapy, there was either a minor response or no response to chemotherapy. In 13 cases where CD10 expression had decreased, 12 cases had a clinical response to chemotherapy. CONCLUSIONS: Strong CD10 expression correlates with hormone receptor negativity and HER-2/neu overexpression. Stromal CD10 expression in breast cancer is not static and changes with neo-adjuvant anthracycline-based chemotherapy. A stable or decrease in CD10 expression correlates with complete or partial clinical response, while an increase in CD10 expression appears to correlate with poor clinical response. A larger series is required to determine the clinical significance of these changes. As stromal CD10 expression and its change with chemotherapy may have a prognostic significance, they should be documented in breast cancer patients before and after chemotherapy.

Biphasic flux profiles of melatonin: the Yin-Yang of transdermal permeation enhancement mediated by fatty alcohol enhancers.

This study investigates physicochemical processes responsible for the biphasic transdermal flux profiles of melatonin in the presence of saturated fatty alcohols (SFAL) and unsaturated fatty alcohols (USFAL). The first phase melatonin flux (J(1st)) in the presence of USFAL enhancers increased with increase in the number of double bonds and reached a limiting value with two double bonds in the molecule. In case of SFAL enhancers, J(1st) increased with enhancer chain length and log formulation/skin partition coefficients (log Ps), which were calculated using the solubility parameters of various formulation components. But, melatonin flux in the second phase decreased with increase in the enhancer chain length and log P values. On the other hand, the transepidermal water loss (TEWL) from the SFAL treated skin increased drastically in the second phase and correlated with log P value of the enhancer. High TEWL value, indicative of a severely disrupted SC, may help the polar formulation components to accumulate in the SC. As a consequence, the SC polarity could change significantly and reduce the partitioning of lipophilic enhancer and/or melatonin in the second phase. This study demonstrated that an optimal level of barrier disruption enhances the transdermal permeation of drugs, whereas, a drastic barrier disruption impedes transdermal transport.

Formulation and in vitro evaluation of transdermal patches of melatonin.

The present study was undertaken to prepare and evaluate monolithic drug-inadhesive type transdermal patches of melatonin containing penetration enhancers such as fatty alcohols, fatty acids, and terpenes. The patches were prepared using Eudragit E 100 as the adhesive polymer. The release profile of melatonin from control as well as enhancer-containing patches showed an initial burst of melatonin release for up to 4 hours and then a plateau after 8 hours. The release profiles of melatonin from patches containing various enhancers were similar to the control patch. However, the addition of enhancers in the patch increased the permeation of melatonin through hairless rat skin. The flux values of patches containing octanol, nonanoic acid, and myristic acid were higher than the control patch (no enhancer), but the differences were not statistically significant (P>0.05). Decanol, myristyl alcohol, and undecanoic acid at 5% concentrations showed significantly higher flux values through hairless rat skin (enhancement ratios 1.7, 1.5, and 1.6 for decanol, myristyl alcohol, and undecanoic acid, respectively) (P<0.05). Menthol and limonene at 5% w/w showed maximum permeation of melatonin among all enhancers studied (enhancement ratios=2.1 and 2.0 for menthol and limonene, respectively) (P<0.001). In general, there was about 4-6 hours of lag time observed before a steady state flux of melatonin was achieved. Though the flux of melatonin observed in the present study is 5-10 times higher than the required delivery rate in humans, it must be noted that the present study was performed using hairless rat skin, which is generally more permeable compared to human skin. Further studies using human skin would prove the usefulness of these patches.