Human breast cancer cell line Hs578T was stably transfected with cDNA for cyclooxygenase-1 or -2. When the cells overexpressing cyclooxygenase-1 or -2 were stimulated with concanavalin A, the processing of matrix metalloproteinase-2 was observed with the aid of gelatin zymography. This processing was not seen in mock-transfected and original cells which did not express detectable cyclooxygenase activity. Furthermore, Northern blotting showed 8^13 fold induction of membrane-type 1 matrix metalloproteinase which processed matrix metalloproteinase-2 in the cells expressing cyclooxygenases. These findings suggest that both isoforms of cyclooxygenase mediate the processing of matrix metalloproteinase-2 through induction of membrane-type 1 metalloproteinase in breast cancer cells.z 1999 Federation of European Biochemical Societies.

1. Whole‐cell voltage‐clamp recordings were made from postnatal rat suprachiasmatic (SCN) neurones to investigate possible modulation by 5‐hydroxytryptamine (5‐HT) of gamma‐aminobutyric acid (GABA)‐activated current (IGABA). 2. 5‐HT reversibly inhibited IGABA in a concentration‐dependent manner (10(‐10) to 10(‐6) M). (+/‐)‐8‐Hydroxy‐2‐N,N‐dipropylaminotetralin (8‐OH‐DPAT, 10(‐10) to 10(‐5) M) and 5‐carboxamidotryptamine (10(‐6) M) also inhibited IGABA, whereas 1‐(2,5‐dimethyl‐4‐iodophenyl)‐2‐aminopropane (DOI, 10(‐6) M) had no significant effect. 3. The effect of 8‐OH‐DPAT (10(‐7) M) was blocked by ritanserin (10(‐7) M), but not by pindolol (10(‐7) M). The effect of 5‐HT was also suppressed by ritanserin, but not by pindolol, ketanserin (10(‐7) M) or ICS 205‐930 (10(‐6) M). 4. 8‐Bromo‐cAMP (10(‐3) M) or forskolin (5 x 10(‐5) M) suppressed IGABA. The effects of forskolin and 5‐HT were not additive. Furthermore, the effect of 5‐HT (10(‐7) M) was significantly reduced by N‐[2‐(methylamino)ethyl]‐5‐isoquinoline sulphonamide (H‐8, 10(‐6) M). 5. It is concluded that 5‐HT inhibits IGABA in the SCN neurones, which involves the activation of 5‐HT7 receptors and cAMP‐coupled systems.

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Sentinel lymphadenectomy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. However, controversies remain concerning the optimal method to identify the sentinel lymph node (SLN) and detect micrometastases in this lymph node. We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of preoperative lymphoscintigraphy with intraoperative dye-guided and gamma probe-guided methods achieves a higher rate of identification of SLN than any of these techniques alone. (b) Immediate and reliable intraoperative assessment of sentinel node status is vital to the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot always be identified. (c) Hematoxylin and eosin (H&E) staining and/or immunohistochemistry on permanent sections are useful for the detection of micrometastases in the sentinel node. Although a reverse transcriptase-polymerase chain reaction (RT-PCR) method is more sensitive than H&E staining and immunohistochemistry, it would not distinguish benign from malignant epithelial cells in the SLN. Therefore, further study is required before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer.

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