About one-third of human breast cancers require hormones for their continued growth and endocrine ablation or anti-hormone therapy can cause regression of these tumours. As a consequence, ovariectomy in premenopausal women or administration of an anti-oestrogen (tamoxifen) in postmenopausal women represent major options for treatment of metastatic breast cancer. Alternatively, chronic administration of agonistic analogues of luteinizing hormone-releasing hormone (LHRH) causes regression of mammary tumours in experimental animals, and such treatment has shown promise in a small series of premenopausal women with advanced breast cancer. It has been assumed that these results were achieved by suppressing the pituitary-ovarian axis, as the treatment causes a reduction in circulating levels of gonadal steroids similar to that produced by castration. However, LHRH agonists can exert major effects on tissues other than the pituitary in animals and in the human. Such findings, coupled with reports of LHRH in human breast milk and immunohistochemical evidence for the presence of LHRH-like activity in some human breast tumours, prompted us to test whether LHRH agonists could have direct antitumour effects. We now report major direct effects of LHRH and its agonists on the growth of breast tumour cells in culture.

Summary The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and transforming growth factor a (TGF-a) was determined in 76 malignant, six borderline and 15 benign primary ovarian tumours using the reverse transcriptase-polymerase chain reaction and related to clinical and pathological parameters. Of the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75) expressed EGF mRNA and 35% (26/75) expressed TGF-a mRNA. For the borderline tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF-a mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15) expressed TGF-a mRNA. The presence of the EGF receptor in malignant tumours was associated with that of TGF-a (P = 0.0015) but not with EGF (P = 1.00), whereas there was no relationship between the presence of EGF and TGF-a (P = 1.00). EGF receptor mRNA expression was significantly and positively associated with serous histology (P = 0.006) but not with stage or grade. Neither EGF nor TGF-a showed any link with histological subtype or stage. The survival of patients with malignant tumours possessing EGF receptor mRNA was significantly reduced compared with that of patients whose tumours were negative (P = 0.030 for all malignant tumours; P= 0.007 for malignant epithelial tumours only). In contrast, neither the expression of TGF-a nor EGF was related to survival. These data suggest that the presence of EGF receptor mRNA is associated with poor prognosis in primary ovarian cancer.

The mucosal epithelium of the toad urinary bladder reabsorbs sodium, acidifies the urine, and is responsive to neurohypophyseal hormnones. Mucosal epithelial cells, consisting of two major morphologic cell types, "mitochondria-rich" and "granular," were removed from the bladder and separated by density gradient centrifugation. The mitochondria-rich cells contained three times as much carbonic anhydrase activity as the granular cells. Oxytocin caused a 235 percent increase in the adenosine 3',5'-monophosphate content of mitochondria-rich cells but had no effect on the granular cells. The evidence indicates that the mitochondria-rich cell, which accounts for only 15 percent of the mucosal cells, plays a major role in the mediation of sodium ion and hydrogen ion transport in the toad bladder and is a specific site of action of neurohypophyseal hormones.

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Forty human cysts have been examined to determine the relationship between the epithelial lining and the content of sodium (Na+) and potassium (K+) in the cyst fluid. The ratios of Na+ to K+ for cysts lined by flattened epithelium were higher in all cases than the values obtained for cysts lined by apocrine epithelium. These findings suggest a morphological basis for the two populations of human breast cyst fluids which can be defined on cationic content.

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We determined inhomogeneity of strains around discontinuities as well as changes in orientation of collagen fibrils under applied load in skin. Second Harmonic Generation (SHG) images of collagen fibrils were obtained at different strain magnitudes. Changes in collagen orientation were analyzed using Fast Fourier Transforms (FFT) while strain inhomogeneity was determined at different distances from hair follicles using Digital Image Correlation (DIC). A parameter, defined as the Collagen Orientation Index (COI), is introduced that accounts for the increasingly ellipsoidal nature of the FFT amplitude images upon loading. We show that the COI demonstrates two distinct mechanical regimes, one at low strains (0%, 2.5%, 5% strain) in which randomly oriented collagen fibrils align in the direction of applied deformation. In the second regime, beginning at 5% strain, collagen fibrils elongate in response to applied deformation. Furthermore, the COI is also found to be linearly correlated with the applied stress indicating that collagen fibrils orient to take the applied load. DIC results indicated that major principal strains were found to increase with increased load at all locations. In contrast, minimum principal strain was dependent on distance from hair follicles. These findings are significant because global and local changes in collagen deformations are expected to be changed by disease, and could affect stem cell populations surrounding hair follicles, including mesenchymal stem cells within the outer root sheath.

All breast cysts aspirated from a series of 100 patients followed for a minimum period of 2 years were classified on the basis of electrolyte composition as apocrine or flattened, this being the nature of the epithelium lining the two populations of breast cysts. Patients with a single cyst were more than 3 times as likely to have a flattened rather than an apocrine cyst. Multiple cysts, whether simultaneous or sequential in any individual patient, were usually all of the same type, and were more commonly apocrine than flattened. A comparison of the frequency of subsequent cysts in patients whose initial cysts were of either apocrine or flattened type showed further cysts were over 5 times more common in patients who presented with apocrine cysts. These observations suggest that the natural history of cystic disease is closely related to cyst type.