The pituitary and luteal responsiveness of GnRH were studied in 20 normal women at different stages of the luteal phase (LP). Blood samples were collected every 15 min for 180 min before and 120 min ...after the iv injection of 25 micrograms GnRH. The studies were performed in the early LP (ELP; days 2-3 of LP; n = 5), mid-LP (MLP: days 4-8 of LP; n = 11), late LP (LLP; days 9-12 of LP; n = 13), and premenstrual phase (PMP; days 13-14 of LP; n = 3). Plasma LH, FSH, progesterone (P), and estradiol (E) levels were assayed by RIA. The data were analyzed as integrated secretory area before (ISAb) and after GnRH stimulation (ISAs) and in terms of their percent increase with respect to the basal value. In all studies, GnRH elicited increases in plasma LH and FSH (P less than 0.001). On the other hand, in the ELP, GnRH did not alter steroid ISAs compared to their ISAb, while significant increases in plasma P and E levels were found in the MLP (P, P less than 0.01; E, P less than 0.02) and LLP (P and E, P less than 0.01). In the PMP, two women had no increase in steroid secretion; in the remainder of the subjects, both P and E ISAs markedly increased. This different pattern was not related to basal steroid levels. All women who had a blunted steroid response in the ELP or PMP had a normal secretory response of both P and E when studied at the other LP stages of the same cycle. Furthermore, there was a positive linear correlation between plasma P and E for the ISAb and ISAs values, while the secretory patterns of gonadotropins and steroids were not related to each other. In conclusion, the corpus luteum is able to respond to GnRH to GnRH at a well identified period of the LP. This pattern indicates variable dependence of the corpus luteum on the functional activity of the hypothalamic-pituitary axis.
Fourteen patients with advanced ovarian carcinoma (FIGO stages III-IV) resistant to cisplatin were submitted to an alternating regimen with doxorubicin (A), cyclophosphamide (C), bleomycin (B) and ...mitomycin C (M). All patients had measurable disease on entry into the study. No responses were observed while 3 patients, previously showing no change in cisplatin, had disease stabilization lasting 3, 4 and 6 months, respectively. All but 1 patient died with a median survival from the start of ACBM therapy of 7 months (range 6-11). ACBM-induced toxicity was remarkable with 50% grade II-III myelotoxicity which required a dose reduction in 43%, treatment delays in 64% and treatment discontinuation in 14%. All patients suffered from mild to moderate nausea and vomiting while reversible alopecia was seen in 42.8%. The lack of response and the substantial toxicity observed suggest that the ACBM regimen in the doses and schedule employed is not beneficial in ovarian carcinoma resistant to cisplatin.
The present study was conducted to explore whether neoadjuvant chemotherapy with a combination of epirubicin, paclitaxel and cisplatin could improve the operability and pathological response rate in ...locally advanced cervical cancer patients.
Between April 1996 and July 2000, 42 patients with carcinoma of the uterine cervix, FIGO stage Ib(2)-IVa, were treated with two or three 21-day cycles of an epirubicin 100 mg/m(2), paclitaxel 175 mg/m(2), cisplatin 100 mg/m(2) regimen.
All patients were eligible for evaluation of toxicity and response. A total of 92 courses of therapy were administered. Three patients had a 20% reduction from the starting dose due to haematological toxicity. Grade 3-4 leukopenia was observed in 15% of cycles, requiring G-CSF support in half of them. Major non-haematological toxicity consisted of grade 3 alopecia (100%), and grade 3 nausea and vomiting (40%). A total of 33 clinical responses (78.5%, 95% CI 63.8-93.2) were recorded, 8 complete responses (CR) and 25 partial responses (PR). Of the 42 patients, 32 (76.2%) underwent radical surgery. At pathological examination 8 complete or microscopic pathological responses, 17 PRs, and 9 patients with stable disease were observed. The median follow-up time was 17 months for the 42 patients enrolled (range 3-62 months). Among the patients submitted to radical surgery, five recurrences were observed, with a median disease-free survival of 47 months. Median overall survival had not been reached at the time of this report. These results appear to be in the range reported for other neoadjuvant cisplatin-based regimens not including paclitaxel.
Neoadjuvant chemotherapy with the epirubicin, paclitaxel and cisplatin combination followed by radical surgery proved to be a safe and effective approach to advanced cervical cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Serum levels of IL-6 were evaluated in a large group of patients with benign or malignant gynecological tumors. The results obtained were correlated with the patients' clinicopathological features ...and follow-up data. Using a highly sensitive immunoenzymatic method for the evaluation of serum IL-6 levels, we observed that > 95% of normal healthy women exhibited values within the range of 1.9-6 pg/ml. Using a cut-off of 6 pg/ml, elevated levels of serum IL-6 were found in 53% of 45 patients with primary epithelial ovarian cancer and less frequently in patients with endometrial and cervical cancer (37% and 10% respectively). Elevated levels of IL-6 were occasionally seen in patients with benign disease. IL-6 serum levels appeared to be less sensitive than CA 125 in ovarian cancer diagnosis. In cancer patients, increased IL-6 serum levels were related to the presence of the tumor since all post-operative patients exhibited a marked decrease. In patients with advanced ovarian cancer post-operative levels of IL-6 correlated with residual disease. Very high levels of IL-6 were observed in the ascitic fluid of 9 ovarian cancer patients, but IL-6 mRNA was not detected in tumor cells. This suggests that the increased production of IL-6 observed in ovarian cancer is reactive. Higher levels of IL-6 were found in patients unresponsive to chemotherapy, as compared with responsive ones. Univariate analysis of survival data suggests that increased IL-6 serum levels correlate with negative prognosis.
Ten patients with polycystic ovary disease (PCOD) had ovulation induction after pituitary suppression by gonadotropin releasing hormone agonist (GnRHa) with GnRHa plus pure follicle-stimulating ...hormone (FSH) or plus human menopausal gonadotropin (hMG). Duration of the stimulation period and gonadotropin doses were superimposable. A multifollicular response was observed in both treatments. Bioassay and radioimmunoassay of luteinizing hormone, androstanedione and testosterone plasma levels were higher in hMG cycles compared to FSH-treated cycles. No differences was found in FSH and estradiol (E2) plasma concentrations, whereas in hMG-treated cycles the E2/number of follicles and E2/ovarian volume ratios were greater than in the FSH-treated cycles. Clinical results in terms of percentages of ovulation and pregnancies were the same in the two protocols. We conclude that the presence of luteinizing hormone in induction of ovulation in patients with PCOD does not seem to influence follicular recruitment and development, but it may have a role in the enhancement of steroid production.
An image analysis method, based on the calculation of the fractal spectrum of leaf colour, was evaluated for its potential use in assessing frost hardiness in plants. The technique developed ...consisted of a) digitization of the leaves after freezing treatments, b) splitting of the images obtained into the three components of the RGB (red, green and blue) colour system and c) calculation of the fractal spectrum for each colour component of the leaf. It was then tested to assess the freezing hardiness of acclimated and non-acclimated Callistemon linearis plants. The analysis system consisted of a scanning device, a personal computer and the image analysis algorithm. All the fractal parameters showed a sigmoidal relationship with temperature. From the inflection point, the LT
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calculated for acclimated and non-acclimated plants, was -7.5 and -4.8°C, respectively. The LT
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calculated from the electrolyte leakage test on the same material was about 2°C warmer than the LT
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obtained from fractal analysis. The role of fractal analysis of leaf colour as an additional, rapid and inexpensive method for identifying freezing damage is discussed.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
We studied the morphological changes induced by 17-b-estradiol (E2) and/or Epidermal Growth Factor (EGF) in an estrogen sensitive human breast cancer cell line (CG5) characterized by a high growth ...responsiveness to EGF and by a single class of high affinity I-125 EGF binding sites. EGF treated cultures showed conspicuous morphological changes consisting of retraction from the substrate, loss of cell-to-cell contacts and expression of surface crest-like and bled protrusions. E2-treated cells showed an increased number of microvilli with respect to control. In cells simultaneously treated with EGF and E2, despite the expression of microvilli, cell surface modifications were similar to those found in the presence of EGF alone, suggesting that EGF may negatively modulate the estrogen-induced morphological changes. In CG5 cells EGF induced a reduction of ER and PR levels and inhibited the estrogen-induced increase of PR. Our findings suggest that the activation of specific EGF-induced intracellular pathways could decrease or modulate those induced by E2.
Serum levels of CA 19-9, CA 125 and CA 15-3 were measured in 91 patients with cervical cancer (16 with intraepithelial neoplasia and 75 with invasive cancer). In 35 patients with locally advanced ...cervical cancer, serum marker levels were measured at monthly intervals during neo-adjuvant chemotherapy. CA 19-9 was found to be abnormally high only in advanced stages with an overall sensitivity of 7.3%. CA 125 and CA 15-3 were elevated in 31.9 and 23.1% of the patients, respectively, with a combined sensitivity of about 40%. The mean values of CA 125 and CA 15-3 were positively related to clinical stage and tumor differentiation. CA 125 and CA 15-3 values were correlated with response to chemotherapy in more than 80% of the cases. These findings suggest that CA 125 and CA 15-3 could be usefully employed in the management of cervical cancer.
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