Matrix Metalloproteinases in Breast Cancer

Abstract: Matrix metalloproteinases (MMPs) represent a class of enzymes able to degrade numerous extracellular matrix macromolecules facilitating tumor invasion and metastasis. The principal MMPs involved in breast pathology are analyzed with their various roles and functions: gelatinases A and B, stromelysin-3, collagenase-3, and MT-MMP1 (membrane type MMP). In vivo and in vitro studies clearly demonstrate an important cooperation between tumor and stromal cells for the expression of these MMPs in breast carcinomas. The large expression of MMPs plead in favor of a major role of these enzymes in breast carcinoma progression and their detection may be used in some cases as a prognostic indicator. Studies now are in progress, directed toward the modulation of these MMPs and their inhibitors with new therapeutic agents to block tumoral invasion and metastasis due to these enzymes.?     

Impairment of bone turnover in elderly women with hip fracture

Summary Hip fracture is one of the most severe consequences of osteoporosis affecting aged women. However, abnormalities of bone turnover responsible for bone loss in this condition have not been clearly defined. To further evaluate the bone metabolic status of women sustaining hip fracture, we have prospectively measured serum osteocalcin as a marker of bone formation and urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-pyr) cross-links as markers of bone collagen degradation in 174 independently living women (80 ± 8 years) within a few hours after a hip fracture. Comparison was made with 77 age-matched controls (80 ± 5 years) and 17 premenopausal women (39 ± 3 years). In addition 15 of the patients were followed with daily measurements during the first postoperative week. At the time of admission osteocalcin was 20% lower in the fractured women compared to the elderly controls (7.6 ± 3.8 vs. 9.5 ± 4.5 nglml,P = 0.001). Pyr and D-pyr were 36% and 40% higher, respectively (P = 0.0001), than in elderly controls and 85% and 76% higher than in premenopausal controls (P = 0.0001). Serum osteocalcin did not correlate with the cortisol level measured at the same time (r = 0.03, ns), nor with serum albumin and creatinine. Serum osteocalcin remained unchanged within 18 hours after fracture, whereafter it progressively decreased until the third postoperative day. No correlation was noted between the excretion of pyridinoline cross-links and the time elapsed from fracture.These data suggest that the abnormal levels of osteocalcin and pyridinolines are unrelated to traumatically induced acute changes, but reflect abnormalities of bone turnover existing prior to the fracture. Thus, hip-fracture patients have biochemical evidence of decreased bone formation and increased bone resorption when compared to age-matched controls. We suggest that these abnormalities may play a role in the decrease of the bone mass and the consequently increased bone fragility that characterize the osteoporotic hip fracture in the elderly.     

Kearns-Sayre syndrome: complete auriculoventricular block, torsade de pointes and ventricular fibrillation

The authors present the case of a new case of Kearns-Sayre syndrome, with early manifestations (7 months) and dramatic cardiac course. They document the ultimate and often fatal stage of the cardiac disorders of this syndrome, which was usually related to an asystole due to a total atrio-ventricular block and represented in this case by a ventricular hyperexcitability (ventricular tachycardia--"torsade de pointes"--ventricular fibrillation) occurring on an atrio-ventricular block; only one previous, undocumented case was found in the literature. The literature is reviewed in order to analyze the nature and chronology of the heart disorders in the course of the disease, and stress the screening modalities and therapeutic indications (continuous heart stimulation).     

Cyclotron production of carrier-free 66Ga as a positron emitting label of albumin colloids for clinical use

A method for producing carrier free ⁶⁶Ga (T_1/2:9.4h; ⁺) by ⁴He bombardment of natural copper targets is presented. ⁶⁶Ga is formed by means of the ⁶³Cu (⁴He, n) ⁶⁶Ga reaction. Production yields are given in the 17.5 to 8 MeV ⁴He energy range. Chemical purification of ⁶⁶Ga from the copper target is described. The only radionuclidic impurity found in the final product was ⁶⁷Ga. Albumin colloids from commercially available kits designed for use with ^99mTc could easily be labeled with ⁶⁶Ga and employed for studies of the lymphatic system by positron emission tomography.     

Concept and technic of malleable subperiosteal onlay. Toward a new dimension in facial rejuvenation surgery

We believe that rejuvenation of the shapes and volumes of the face is just as important as "tightening of the skin and muscles". In this way a more complete rejuvenation effect is obtained which is better perceived by others. The SMO technique provides a solution by the use of malleable coral microgranules, which may constitute the first biomaterial of a new generation of plastic and malleable onlays. In this context, a more general volumetric concept of ageing is developed, leading to a modification in our consultation and our treatment. Most importantly, this approach opens a whole new field, that of preventative treatment of facial ageing, which will no doubt be multidisciplinary.     

Comparison of cord blood immunoglobulin E concentrations and maternal allergy for the prediction of atopic diseases in infancy

Total serum IgE levels were determined in 136 newborns and their mothers and in 54 of their fathers, using the paper radioimmunosorbent test (PRIST) technique. IgE specific antibodies for house dust (Dermatophagoides pteronyssinus), orchard grass, timothy grass, and cow's milk were measured with the radioallergosorbent test (RAST). One hundred thirty-three RAST assays were negative in newborns, and in three cases RAST for cow's milk was positive. Cord blood IgE ranged from 0 to 5.5 IU/ml (mean 0.32 ± 0.54 IU/ml); levels were significantly (p < 0.05) higher when maternal IgE was over 100 IU/ml and when mothers had received progesterone therapy during the pregnancy. Salbutamol administration or tobacco smoking during pregnancy did not influence newborn IgE. A clinical follow-up study was conducted in 83 infants for 9 mo. Nine infants developed definite atopic disease, and possible allergic diseases were noted in eight other infants. The IgE level at birth appeared to be more predictive for the development of allergy in infancy than the family history.     

Role of angiotensin in the salt-hypertension of rats

Summary Hypertension was induced in uninephrectomized rats by NaCl 0.9% drinking and deoxycorticosterone acetate (DOCA) administration for 6 weeks. Plasma renin activity was markedly reduced but not suppressed. Renal renin concentration and total renal renin content were moderately reduced. Intravenous injection of 0.2 ml of antiangiotensin plasma resulted in transitory hypotension both in salt and DOCA-treated rats, and in normotensive control rats. It is concluded that angiotensin participates in the maintenance of blood pressure in salthypertensive rats as well as in normal animals.This work was supported by grant 67-00-517 from D.G.R.S.T. (Délégation Générale à la Recherche Scientifique et Technique). The authors wish to thank Miss colette Innocenzi and Miss Sonia Culot for technical assistance.