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Biomedical subjects

N Biglia

Publications and source records attributed to N Biglia.

At least 37 records · Page 2Linked to original sources
PubMed1997

Progestins and breast cancer risk.

There is still no clear account on the role that progestins play in human breast cancer, and the issue continues to be debated. The effects of progestins on breast cell proliferation have been investigated in a number of different experimental systems with conflicting results. Progesterone has been reported to both stimulate and inhibit the growth of experimental mammary tumors, depending upon the dose and the experimental models. Epidemiological studies on the effect of combined hormone replacement therapy (HRT) on breast cancer risk in menopausal women are limited because the use of a progestin in addition to estrogens was not widely adopted until 10 years ago. Taking meta-analysis into account estrogen-progestin use did conclude that there is not an excess risk in combined HRT users. Epidemiological studies have provided conflicting results, ranging from a protective effect to a deleterious effect of progestin addition on breast cancer risk. Progestins include a large family of molecules characterised by different binding capacities to androgen receptors. This implies that they should be considered as distinct yet related, therapeutic agents. The use of different progestins may account for the controversial results obtained in studies conducted in different geographic areas.

Animals↗
PubMed1995

Potential impact on breast cancer risk of circulating insulin-like growth factor I modifications induced by oral HRT in menopause.

Unlike parenteral estrogens, oral estrogen administration in menopause causes, through its hepatocellular action, a significant decrease of circulating insulin-like growth factor I (IGF-I) levels; this effect is opposed by the addition of an androgenic progestogen. In vitro studies show that IGF-I is a potent mitogen for 'estrogen responsive' breast cancer cells. Moreover, some findings in breast cancer patients and in women treated with tamoxifen suggest that reduction of circulating IGF-I could be protective to the breast. However, by also considering (1) the potential action on breast cancer cells of IGF-II, (2) the possible consequences of the growth hormone (GH) increase caused by the IGF-I reduction and (3) the fact that in vitro results are not simply transferable to the in vivo condition, other 'scenarios' can be envisaged, besides the favorable one. In support of the latter, there are epidemiologic data which suggest that oral estrogen use could have some favorable peculiarities with regards to breast cancer risk. The associated decrease in circulating IGF-I level could well be one of these peculiarities.

Breast Neoplasms↗
PubMed1994

Androgenic progestogens oppose the decrease of insulin-like growth factor I serum level induced by conjugated oestrogens in postmenopausal women. Preliminary report.

Oral oestrogen treatment in postmenopausal women causes a decrease of insulin-like growth factor I (IGF-I) serum level, probably through a hepatocellular effect. To explore the possibility that the androgenic progestogens oppose this effect, serum IGF-I and sex hormone binding globulin (SHBG) were evaluated in two groups of patients treated respectively with oral conjugated oestrogens (oCE) or transdermal oestradiol (tdE2), in a first phase with the addition of dydrogesterone (DYDR), a non-androgenic progestogen, and subsequently with the addition of norethisterone acetate (NETA). With respect to basal values, treatment with oCE+DYDR caused an increase of SHBG (P < 0.002) and a decrease of IGF-I serum levels (P < 0.05); the shift to NETA addition opposed both effects: SHBG levels decreased partially but significantly (P < 0.01 vs. oCE + DYDR) and IGF-I returned to basal values with a significant increase with respect to the oCE + DYDR phase (P < 0.02). No changes were observed in the tdE2 + DYDR treated women; in this group the shift to NETA addition caused a significant decrease of SHBG values (P < 0.001 vs. before treatment and vs. tdE2 + DYDR phase) and a slight increase of IGF-I values. These differential effects on IGF-I and SHBG serum levels might be relevant as far as breast cancer risk is concerned.

Administration, Cutaneous↗
PubMed1994

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.

Breast Neoplasms↗
PubMed1993

Differential effects of oral conjugated estrogens and transdermal estradiol on insulin-like growth factor 1, growth hormone and sex hormone binding globulin serum levels.

In postmenopausal women oral ethinylestradiol causes a reduction in circulating insulin-like growth factor 1 (IGF-1) and an increase in serum growth hormone levels. There are no data on the effect of conjugated estrogens, the preparation most often used in estrogen replacement treatment (ERT), on these parameters. We evaluated serum IGF-1 and growth hormone levels, together with the levels of sex hormone binding globulin (SHBG), an indicator of estrogen hepatocellular action, before and after 6 months of ERT in two comparable groups of postmenopausal women. Sixteen women were treated with oral conjugated estrogens, 0.625 mg/day, and 14 with transdermal estradiol, 0.05 mg/day. In the women treated with oral conjugated estrogens, an increase in SHBG (p < 0.001), a decrease in IGF-1 (p < 0.001) and an increase in growth hormone (p < 0.05) serum levels were observed. No such effects were seen with the use of transdermal estradiol, devoid of hepatocellular effects. Undoubtedly, oral conjugated estrogens, 0.625 mg/day, through a hepatocellular effect, cause marked modifications in the IGF-1/growth hormone axis, which may have clinical relevance. For instance, the decreased IGF-1 level, together with the increased level of SHBG, might provide some explanation of the favorable epidemiological data on breast cancer risk in women receiving oral conjugated estrogens.

Administration, Cutaneous↗
PubMed1992

Post-menopausal breast cancer risk: oral estrogen treatment and abdominal obesity induce opposite changes in possibly important biological variables.

Almost all of the epidemiological studies on the consequences of estrogen replacement treatment (ERT) refer to subjects treated with oral conjugated equine estrogens (CEE). These studies suggest that breast cancer (BC) risk is limited and can only be seen after long-term and/or high dosage use. Orally administered estrogens present a number of metabolic and endocrine peculiarities, some of which could be important in reducing the risk to the breast. Actually, these peculiarities are opposite to those observed in post-menopausal women with abdominal obesity (AO), a group which has recently been identified to be at high risk. AO (as other situations in which an increase in BC risk does exist) shows a sex-hormone-binding-globulin (SHBG) level reduction, which causes an increase of both estrogenic and androgenic activity. Further features of AO, possibly involved in BC risk, could be: i) increased free fatty acid (FFA) levels; ii) hyperinsulinemia; iii) increase of circulating insulin-like growth-factor-I (IGF-I) activity. On the contrary oral estrogens, through their hepatocellular effects, cause: i) a clearcut SHBG increase; ii) a trend to reduced circulating IGF-I activity. As a consequence, the possibility that oral estrogens are characterized by a favourable balance between estrogenic activity and biological modifications protective to the breast, is worth consideration. Even non-oral estradiol have a possible protective action through FFA level reduction; however, due to the absence of hepatocellular effect, it does not influence SHBG levels and IGF-I activity. It seems difficult to extend data on the relationship between BC and oral CEE to other types of types of ERT. For the latter, further study will be necessary.

Breast Neoplasms↗
PubMed1991

Chemoresistance in breast tumors.

Resistance to multiple chemotherapeutic agents is a common clinical problem in the treatment of cancer: such resistance may occur in primary therapy or be acquired during treatment. The most commonly used antineoplastic agents in the treatment of disseminated breast cancer are adriamycin, methotrexate and cyclophosphamide. Cell lines selected for resistance to adriamycin often develop cross-resistance to structurally dissimilar antineoplastic drugs with different mechanisms of cytotoxic action; this phenomenon has been called pleiotropic or multidrug resistance (MDR). In vitro models of MDR have shown that this type of resistance is accompanied by a decrease in cellular drug accumulation, mediated by the over-expression of a 170 kD plasma membrane glycoprotein referred to as P170. Glycoprotein P170 is an energy-dependent multidrug efflux pump, whose activity can be inhibited in vitro by a variety of agents including verapamil, quinidine and reserpine. P170 is over-expressed also in some human malignancies, and evidence exists about its role in examples of clinical resistance in vitro. Clinical trials using verapamil, a calcium channel blocker which selectively enhances drug cytotoxicity in MDR cell lines, have been prompted for leukemia and ovarian cancer. In addition other approaches are the subject of current preclinical investigations. Several observations as well the phenomenon of "atypical" MDR in cell lines which do not overexpress P170, suggest that also other factors are involved in multidrug resistance. Qualitative or quantitative changes in the activity of topoisomerases, protein kinase-related systems and glutathione S-transferase, may confer pleiotropic resistance. As the role of these genes and their regulation is clarified, they may also serve as useful targets for pharmacologic intervention in the treatment of drug-resistant human tumors. The mechanisms involved in resistance to methotrexate and cyclophosphamide are less studied, particularly in vivo samples. Methotrexate resistance is probably a complex multifactorial phenomenon; in some cases it is due to an increase in the expression of the drug target dihydrofolate reductase, often as a result of gene amplification, but in other cases a transport defect of the methotrexate or alterations of the activity of different enzymes have been reported. Cyclophosphamide (CP) resistance has been attributed to an increased activity of two different enzymes, glutathione S-transferase, also involved in MDR phenotype, and aldehyde dehydrogenase, which catalyzes inactivation of CP in non cytotoxic metabolites. This paper reviews the current state of our knowledge of chemo-resistance and the utility of available markers to identify potentially resistant tumors in vivo; the strategies that might be used to overcome this phenomenon are also described.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

[Postoperative infections and antibiotic prophylaxis in radical hysterectomy. Review of the literature].

Postoperative infectious complications are a frequent cause of morbidity and mortality in the surgical patient. The septic events usually involve the urinary or respiratory tracts or occur at the operative site. The incidence depends on the surgeon's experience, the surgical procedure applied and the clinical status of the patient. Radical hysterectomy with pelvic lymphadenectomy is associated with a high risk of postoperative infections. Factors that influence the risk are prolonged preoperative hospitalization, duration of operation, younger age, obesity, estimated blood loss and lack of antibiotic prophylaxis. Appropriate administration of prophylactic antibiotics requires awareness of the following considerations: the choice of antibiotic agent, the dosage and the timing of administration for maximum benefit without adverse effects. In this review we evaluate the results of studies that use different regimens of antibiotic prophylaxis for prevention of infectious morbidity after radical hysterectomy.

Anti-Bacterial Agents↗
PubMed1991

[Postoperative infections and antibiotic prophylaxis in radical hysterectomy. Retrospective study].

Radical hysterectomy is associated with a high risk of postoperative infectious morbidity. A series of 73 patients who underwent abdominal radical hysterectomy with pelvic lymphadenectomy is presented. Hospital charts were reviewed to determine the influence of surgical characteristics and of different antibiotic prophylaxis regimens on postoperative septic complications. The overall incidence of postoperative infections was 31.5%; in 13 patients had urinary tract infections (17.7%), 3 surgical site-related infections (4.1%) and 6 febrile morbidity (8.2%). There were also 3 cases of phlebitis and 3 infectious events at distant sites. No interaction was observed between the examined risk factors and the overall infectious morbidity. Time of surgical procedure and average blood transfusion show a trend toward increased values in patients with complications compared to patients with regular postoperative course. The most important current controversy about the use of prophylaxis in radical hysterectomy concerns the duration of postoperative treatment. In this series the major part of the subjects received a long-term antibiotic prophylaxis regimen (greater than 72 hours), and only 18% received a perioperative prophylaxis. Women without postoperative complications were more frequently treated with a long-term antibiotic prophylaxis (82%) compared to women with infectious morbidity (65%). Moreover, in patients with complications, the proportion of cases who needed an additional antibiotic therapy was lower in the group receiving long-term prophylaxis (20%) compared to the short-term group (83%).

Anti-Bacterial Agents↗
PubMed1988

Distribution of Ha-RAS-1 proto-oncogene alleles in breast cancer patients and in a control population.

The frequencies of 13 different Ha-ras proto-oncogene alleles have been estimated in 92 breast cancer patients and 60 unaffected individuals. The Ha-ras alleles can be identified using a DNA restriction fragment length polymorphism (RFLP) closely linked to the 3' end of the gene, and are characterized by a different length due to a region of sequences repeated a variable number of times (variable tandem repeats, VTR). The statistical analysis of the data obtained shows that the frequency of alleles ranging between specific length limits is significantly higher in breast cancer patients than in controls. The same applies to specific genotypes bearing the aforementioned alleles. This suggests that the inheritance of these alleles may be associated with an increased risk of developing breast cancer.

Adult↗