Minced umbilical cord fragments as a source of cells for orthopaedic tissue engineering: an in vitro study.

A promising approach for musculoskeletal repair and regeneration is mesenchymal-stem-cell- (MSC-)based tissue engineering. The aim of the study was to apply a simple protocol based on mincing the umbilical cord (UC), without removing any blood vessels or using any enzymatic digestion, to rapidly obtain an adequate number of multipotent UC-MSCs. We obtained, at passage 1 (P1), a mean value of 4, 2 × 10(6) cells (SD 0,4) from each UC. At immunophenotypic characterization, cells were positive for CD73, CD90, CD105, CD44, CD29, and HLA-I and negative for CD34 and HLA-class II, with a subpopulation negative for both HLA-I and HLA-II. Newborn origin and multilineage potential toward bone, fat, cartilage, and muscle was demonstrated. Telomere length was similar to that of bone-marrow (BM) MSCs from young donors. The results suggest that simply collecting UC-MSCs at P1 from minced umbilical cord fragments allows to achieve a valuable population of cells suitable for orthopaedic tissue engineering.

The influence of hormone replacement therapy on the pathology of breast cancer.

AIM OF THE STUDY: To assess whether the pathological characteristics of breast carcinomas arising in post-menopausal women who ever used hormonal replacement therapy (HRT) differ from those of post-menopausal patients who never used HRT. MATERIALS AND METHODS: Six hundred and forty three consecutive breast cancer patients were entered in a case control-study. Cases were represented by 111 breast cancer patients who had used or were using HRT at the time of diagnosis, while the remaining 532 patients who never used HRT were chosen as controls. RESULTS: Tumour diameter was smaller in HRT users (17.6 vs 22.1 mm; p=0.002) and tumours of lobular histology were almost twice more frequent among HRT users as in 'never users' (21 vs 12%; p=0.01). No differences were found in grading, hormonal receptor status and axillary nodal status. The expression of c-erb B-2, p53, Ki67 and PS2 measured by immunohistochemistry was similar in the two groups. CONCLUSIONS: Our findings suggest that HRT use may modify the pathological presentation of breast cancer. Further studies are indicated, while other clinical-pathological characteristics did not differ according to HRT use.

Management of risk of breast carcinoma in postmenopausal women.

Breast carcinoma is the most frequent tumor in the female population. Many factors can influence the risk of breast cancer; some of them, such as old age and breast cancer 1/2 (BRCA1/BRCA2) gene mutations, are associated with a fourfold increase in risk. A previous diagnosis of atypical ductal or lobular hyperplasia or having a first-degree relative with a carcinoma are factors associated with a two- to fourfold increase in risk. A relative risk between 1 and 2 is associated with longer exposure to endogenous hormones as a result of early menarche, late menopause and obesity, or with recent and prolonged use of hormone replacement therapy (HRT) or with behavioural factors such as high alcohol and fat intake. Is it possible to modify breast cancer risk in postmenopausal women? Risk factors related to lifestyle can be changed, even if it is not clear whether modifying these behavioural factors during the postmenopausal period will influence the overall breast cancer risk. For instance, the influence of exogenous hormones throughout life (both oral contraceptives and HRT) should be evaluated according to the individual risk-benefit ratio. The problem is even more complex for women who carry genetic mutations and for those who have close relatives with breast cancer, who may be candidates for risk reduction strategies. Prophylactic bilateral mastectomy is still controversial, but is frequently offered to or requested by this group of women and may be indicated in BRCA1/BRCA2 carriers. Chemoprevention with tamoxifen and with the new selective estrogen receptor modulators, namely raloxifene, is very promising and deserves a thorough discussion for all high-risk women.

Paclitaxel administration on days 1 and 8 every 21 days in anthracycline-pretreated metastatic breast cancer patients. A multicenter phase II trial.

Paclitaxel is now included in second- and even first-line regimens in advanced breast cancer. The optimal dose and schedule of this drug, however, still remain a matter of investigation. A group of 57 consecutive patients with advanced breast cancer previously treated with anthracycline-containing regimens were submitted to treatment with single-agent paclitaxel administered at 130 mg/m2 on days 1 and 8 every 21 days. Of the 57 patients, 56 were fully evaluable, and of these 25 had an absolute anthracycline resistance, 14 a relative resistance and 17 were potentially sensitive. The median age of the patients was 57 years (range 33-71 years), their median performance status was 1 (0-3), and 27 (47%) had liver involvement, 17 (30%) lung involvement, 30 (53%) bone involvement and 15 (26%) skin/lymph node involvement. Toxicity was recorded in 295 cycles. This scheme was well tolerated, the dose-limiting toxicities being hematological and neurological. Grade 3/4 leukopenia was observed in 20% of patients at nadir, while grade 3 leukopenia was observed in 3% of patients at recycle. Only one patient experienced febrile neutropenia. Grade 2/3 neurotoxicity was observed in 26% of patients, leading to drug withdrawal in three. The treatment was given on an outpatient basis in all patients and the median relative dose intensity of 86.6 mg/m2 per week was 100% of the planned dose (range 75-100%). Three patients (5%) attained a complete clinical response and 12 (21%) a partial response for an overall response rate of 26% (95% confidence interval 18-38%), while 30 (53%) attained disease stabilization and 11 progressed (19%). Time to progression in responding patients was 10.3 months, and the median overall survival of the entire population was 15.4 months. To conclude, paclitaxel administration on days 1 and 8 every 21 days was active and manageable in advanced breast cancer patients previously treated with anthracyclines. The response obtained was durable.

GnRH analogs in benign breast disease and breast cancer chemoprevention. A challenge for the year 2000.

GNRH analogs (GNRHAs) are currently used in the treatment of prostatic and breast cancer and in several benign gynecological conditions. Because of their ability to suppress sex hormone secretion and the supposed role of these hormones in the physiopathology of fibrocystic mastopathy, GNRHAs have been proposed for the management of severe breast pain and nodularity. In preliminary studies the treatment with GNRHAs for 3-6 months improves clinical and radiologic manifestations of mastopathy, also when breast pain has been recurrent or refractory to other hormonal drugs. Further studies are required to determine the optimal length of treatment and the adverse effects induced by estrogen deficiency in premenopausal women. There is evidence that an early menopause reduces woman's lifetime risk of breast cancer. According to this data, a high-dose GNRHAs regimen associated with estrogen replacement therapy (ERT) has been proposed as chemopreventive agent for premenopausal women at high risk of breast cancer. The definition of the long term effects of GNRHAs on bone and lipid metabolism is essential before a large trial of chemoprevention can be carried out.

[LHRH-analogues: clinical results in ovarian and breast cancer]. / Analoghi dell'LHRH: risultati clinici nel carcinoma della mammella e dell'ovaio.

The paper reviews the studies published between 1982 and 1989 on the subject of the use of LHRH analogs in gynecological oncology. Following the analysis of hormonal changes induced by analogue therapy in premenopausal women with advanced stage breast cancer, the clinical results obtained through the clinical treatment of this neoplasia are reported. Results to date are encouraging and analogue therapy still represents an alternative to surgical sterilisation. The clinical findings in postmenopausal women are less encouraging. In both pre- and postmenopause groups, findings were correlated to the receptorial status and site of metastases. The possibility of associating analogues to other hormone replacement therapies, or to chemotherapy is then discussed. Lastly, preliminary data concerning the use of analogue therapy in advanced-stage ovary cancer are analysed. The current indications for therapy and problems still to be resolved concerning the use of LHRH analogue therapy in the context of gynecological oncology are summarised by way of conclusion.

[The use of LHRH analogs in gynecologic oncology]. / L'impiego degli analoghi dell'LHRH nell'oncologia ginecologica.

The use of LHRH analogues in gynecological oncology is related to the capacity of these compounds to determine pharmacological sterilisation which represents an alternative to surgical ovariectomy in the treatment of hormone-sensitive carcinoma. The modes of administration, metabolism and mechanisms of action of these drugs are illustrated. A section of the action of these drugs are illustrated. A section of the work is dedicated to the side-effects; they are divided into adverse effects, in the accepted meaning of the term, and the consequences of secondary hypoestrogenism. The paper concludes with the presentation of experimental data, both in animal studies and in vitro, which are the basis for the use of analogue therapy in the treatment of advanced stage breast cancer.