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PubMed1984

[Echocardiographic study of the left ventricular mass-dilatation ratio in hypertensive disease].

The object of this work is the exhaustive interpretation of 52 echocardiograms of hypertensive African subjects. The following parameters were measured on the echocardiogram: Dd (left ventricular end diastolic dimension), Ds (left ventricular end systolic dimension), DSd (interventricular end diastolic dimension), DEd (left ventricular posterior wall end diastolic thickness). Left ventricular performance was evaluated with the calculated Vcf, FR (fractional shortening) and EF (ejection fraction). A ratio "R" was estimated as he ratio of the left ventricular mass (MVG) measured with Bennett's formula: [(Dsd + DEd + Dd)3-Dd3] x 1,05] to the left ventricular end diastolic dimension. A carotid pulse and phonocardiogram were simultaneously recorded and systolic time intervals were measured and corrected for heart rate, using regression equations corresponding to African subjects. The analysis of the "R" ratio has led us to put forward a new concept of the progression of the hypertensive cardiomyopathy. It has been shown, in this study, that the hypertensive heart becomes hypertrophic, even under treatment and after return of blood pressure to normal. It appears that hypertrophy is a reaction tending to keep normal or almost normal the telediastolic left ventricular dimension and consequently to prevent left ventricular dilatation. This can be explained by the tendency of myocardial hypertrophy to reduce wall stress and oxygen consumption. The analysis of the correlation between MVG and Dd (good), TAM (mean arterial blood pressure) and Dd (poor) and TAM and MVG (nil) has les us to the conclusion that the stimulus to hypertrophy lies in the left ventricular dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomegaly↗
PubMed1984

[Metastatic breast cancer: a comparative study of the efficacy of tamoxifen and the sequential administration of tamoxifen and medroxyprogesterone acetate].

Seventy-nine patients with an histologically proven disseminated breast cancer, never treated before with additive hormonal therapy, entered into a randomized trial between june 1981 and december 1982. In the first group 44 patients were given continually a daily dose of tamoxifen (TAM) of 20 mg/m2. In the 2nd group 35 patients were given a daily dose of TAM of 20 mg/m2 for 15 days and then an oral daily dose of medroxyprogesterone acetate of 350 mg/m2 for the next 15 days. In both groups I and II, the treatment was stopped at the first manifestation of progression of the disease. The hormonal receptor status was determined in 30 patients of the group I and 23 patients of the group II. An objective response to treatment was observed in 48 per cent of the patients of the group I and 60 per cent of the group II. This difference is not significant (X2 = 1,05). However, the mean duration of therapeutic response is significantly higher in the group II (p = 0,01).

Adenocarcinoma↗
PubMed1984

[Urea and arginase activity in rat liver during the administration of thioacetamide].

The authors measure the concentration of urea and arginase activity at pH 6.5 and 9.7 in the rat liver at intervals during the administration thioacetamide (TAM) at a dose of 50 mg per kg of body weight and per day. The values obtained correlate the amount of urea and the arginase activity at pH 6.5 and 9.7 during TAM administration for the intervals comprised between 1-12 days and 12-30 days. These results suggest that the concentration of liver urea depends mainly of the level at arginase activity, which is regulated by the proton concentration of the internal environment.

Acetamides↗
PubMed1981

Biochemical genetics of trehalose metabolism in Saccharomyces cerevisiae.

Different strains of Saccharomyces cerevisiae exhibit alternative patterns of trehalose accumulation during growth on a glucose medium. The active pattern is designated as TAC(+) phenotype and the alternative, low-activity pattern as tac(-) phenotype. The tac(-) phenotype is expressed only during growth, since tac(-) strains actively accumulate trehalose during incubation in a glucose medium lacking a nitrogen source. The tac(-) phenotype appears to be determined by a single, recessive gene tac1. The quantitative expression of the dominant, alternative allele TAC1 is subject to wide variation. A highly active pattern of trehalose accumulation requires TAC1 and an amplification factor, TAM, which consists of one or more dominant gene(s). TAM does not appear to alter significantly the expression of tac1. Highly amplified TAC(+) strains may contain a labile factor not present in a TAC(+) strain which accumulates intermediate levels of trehalose.

Cells, Cultured↗
PubMed1995

Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission: factors predictive of survival, relapse and graft-versus-host disease.

Between 1983 and 1993, 42 patients with acute lymphoblastic leukemia (ALL) in second complete remission (CR) underwent an allogeneic HLA-identical bone marrow transplant (BMT; there was one family mismatched graft). The conditioning regimens varied, consisting of cyclophosphamide (CY) and total body irradiation (TBI; n = 10); CY, TBI, Ara C, VP-16 (n = 11); TBI, Ara C, melphalan (n = 20) (TAM) or other (n = 1). Cyclosporine A (CsA) (n = 15) or CsA and methotrexate (MTX) (n = 24) were the main regimens for prophylaxis of graft-versus-host disease (GVHD). Nineteen of 42 patients are alive in CR ranging from 1 to 72 months after BMT with a median follow-up of 36 months. The 4-year actuarial survival rate was 53%. The actuarial relapse rate was 17%. Twenty three patients died: 4 patients of leukemic relapse, 9 of infection, 2 of acute GVHD, 2 of multiorgan failure after chronic GVHD, 2 of a secondary tumour and 4 patients died of other causes. Several pre- and post-transplant characteristics were analyzed to determine predictive factors for survival, relapse and GVHD. The relapse rate was significantly influenced by the type of conditioning regimen with no relapse in the TBI, Ara C, melphalan group. The analysis of long-term sequelae shows that there are no severe complications in this last group. Our results confirm that allogeneic BMT can lead to long-term survival for children with ALL in second CR and suggest an advantage of using the TAM conditioning regimen in the eradication of the leukemic disease.

Actuarial Analysis↗
PubMed1995

[Electromyographic study of human extrinsic laryngeal muscles].

Seven cases of human extrinsic laryngeal muscles were studied to determine the electrical activities during phonation, coughing, swallowing, fixation of thorax and respiration. The activities of these muscles all fired during phonation which were synchronous with discharge of the thyroarytenoid muscle (TAM) and increased with increasing volume of voice. They also fired during cough reflex and sphincteric action of larynx, and were basically synchronous with the TAM. They were weak during normal respiration. Although stronger electrical activities were recorded during inspiration in dyspnea, they were weaker than discharge during phonation, cough reflex and sphincteric action of larynx.

Adult↗
PubMed1995

[Circumvention of cisplatin resistant ovarian cancer cells by antiestrogens].

Antiestrogens (AEs) have been considered to elicit antitumor effects via estrogen receptor. However, recent reports have demonstrated that AEs had an antitumor effect even in cases without estrogen receptor, and that AEs caused various kinds of biological behavior such as a chemosensitizing effect. We therefore investigated the possibility of circumvention of cisplatin (CDDP) resistance due to the chemosensitizing effect of AEs by using 5 ovarian cancer cell lines. They were named KF, MH, KK, KFra and KFrb cell lines. KF and MH were derived from serous cystadenocarcinomas, and KK from a clear cell carcinoma. KFra and KFrb were CDDP-resistant cell lines developed from the KF cell line. MCF-7 cell line derived from breast cancer was used as a control. The study of a 50% inhibitory concentration (IC50) revealed that clomiphene (CLO) had the most potent antiproliferative effect among the AEs used, and was followed by tamoxifen (TAM) and toremifene (TOR) with a similar effect. On the whole, the degree of CDDP sensitivity was not correlated with the degree of AE sensitivity. KFra cell line which had the highest CDDP-resistance among the 5 ovarian cancer cell lines used was the most sensitive to AEs, especially to CLO. In the study on the combined administration of CDDP and AEs, 1 microM of CLO significantly reduced the IC50 of CDDP to KFrb, KK and MCF-7 cell lines. Similarly, 1 microM of TAM significantly reduced the IC50 of CDDP to KF, KFra and MCF-7 cell lines, and 1 microM of TOR significantly reduced it to KFra, KK and MCF-7 cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Cisplatin↗
PubMedDate not supplied

Direct antiproliferative effect of triptorelin on human breast cancer cells.

We investigated the effect of Triptorelin (Decapeptyl, DEC) alone or combined with Tamoxifen (TAM) or Medroxyprogesterone acetate (MPA) in human breast cancer cells. DEC did not affect the growth of estrogen-insensitive MDA-MB-231 cells, while it inhibited the estrogen-stimulated proliferation of MCF-7 and CG-5 cells. No amplification of growth inhibition induced by TAM or MPA was determined by DEC. Progesterone receptor levels of CG-5 cells were significantly enhanced by DEC in the presence of 17 beta-estradiol (E2) with respect to those in control and E2-treated cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Efficacy of combination therapy consisting of cyclophosphamide, adriamycin, UFT and oophorectomy/tamoxifen for advanced or recurrent breast cancer].

Combination therapy consisting of cyclophosphamide (CPA), adriamycin (ADR), UFT and endocrine therapy of oophorectomy or tamoxifen (TAM) was given female patients with advanced or recurrent breast cancer. Premenopausal patients initially underwent oophorectomy, then were administered 300 mg/day of CPA and 30 mg/day of ADR intravenous injection every 2 weeks, and 300 mg/day of UFT orally every day. Postmenopausal patients, on the other hand, were administered the same three chemotherapeutic drugs and 30 mg/day of TAM orally every day instead of receiving castration. A total of 10 patients were registered, and nine of them were eligible. Premenopausal cases were six, and postmenopausal cases were three. The objective response rates were 50% (3/6) for premenopausal women and 33% (1/3) for postmenopausal women. Complete response was observed in one patient and partial response in three patients. The therapy was effective for lymph nodes (2/2), lung (3/4), breast (2/3), skin or subcutis (1/2), but it showed no effect on bone, pleural effusion or ascites. The overall 5-year survival rate was 53.3%. The main side effects of more than Grade 1 were leucopenia 33% (3/9), anorexia 22% (2/9) and malaise 22% (2/9). They were relatively mild for therapy involving ADR. This therapy was considered useful for advanced or recurrent breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

The effect of droloxifene on the insulin-like growth factor-I-stimulated growth of breast cancer cells.

Insulin-like growth factor-I (IGF-I) is an important mitogen in breast cancer. We studied here the effects of a new antiestrogen drug, droloxifene (DROL, (E)-alpha-[p-[2-(dimethylamino) ethoxy]-phenyl]-alpha'-ethyl-3-stilbenol) and tamoxifen (TAM) on the IGF-I-stimulated growth of estrogen receptor (ER) positive breast cancer cells, MCF-7 and their mechanism of action. IGF-I secretion from MCF-7 was increased by the addition of estrogen. Externally added IGF-I stimulated the growth of MCF-7 but not ER negative breast cancer cells, MDA-MB-231. DROL and TAM inhibited the IGF-I-stimulated growth of MCF-7. A 2 hr treatment with both drugs did not block IGF-I binding to the receptors in MCF-7. However, a 4 day treatment with DROL decreased the number of IGF-I receptors without altering the binding affinity in MCF-7. These results suggest that DROL can exert its antitumor activity against ER positive breast cancer not only by blocking the E2 binding to the ER, but also by counteracting the mitogenic effect of IGF-I.

Antineoplastic Agents↗
PubMed1993

Trial of aminoglutethimide vs hydrocortisone as second-line hormone treatment of advanced breast cancer.

In a randomized trial of second line hormone therapy 56 postmenopausal women with advanced breast cancer received low dose aminoglutethimide (AGT) 125 mg twice daily without hydrocortisone (27 patients), or hydrocortisone (HC) 20 mg twice daily (29 patients). The two groups were well-matched for previous response to tamoxifen (TAM) therapy (AGT (35%) vs HC (32%)) and for relapse on adjuvant TAM. The mean age of the two groups was 69.2 years (AGT) and 63.2 years (HC). Liver metastases were present in 29% (AGT) and 33% (HC). The response rates were 11% (AGT) and 21% (HC). At 12 months the failure of treatment rate was 80% (AGT) and 70% (HC). Survival at 12 months was 50% for both groups. At 12 months 5/12 survivors were still on AGT and 8/12 on HC. These preliminary findings have so far failed to show any statistical difference in tumour response, time to treatment failure or survival between low-dose AGT and HC as second-line hormone treatment post-tamoxifen in advanced breast cancer.

Aged↗
PubMedDate not supplied

Effect of promegestone, tamoxifen, 4-hydroxytamoxifen and ICI 164,384 on the oestrone sulphatase activity of human breast cancer cells.

In the present study, we explored the effects on sulphatase activity by Promegestone (R-5020), Tamoxifen (TAM), 4-hydroxytamoxifen (4-OH-TAM) and ICI 164,384 in the T-47D hormone-dependent and MDA-MB-231 hormone-independent mammary cancer cell lines. Using homogenates of these cells it was observed that Promegestone has a significant effect on the inhibition of oestrone (E1) sulphatase activity. As this effect is competitive, it is suggested that there is a direct action of this compound on the enzyme. Tamoxifen has very little or no effect, 4-hydroxytamoxifen has an intermediate effect and ICI 164,384 is active in the enzyme inhibition, particularly with MDA-MB-231 cells. The present data could open new possibilities for human breast cancer treatment, as sulphatase is very active in the first step of the conversion of oestrone sulphate (E1S) to oestradiol (E2), and oestradiol is one of the principal carcinogenic factors in human hormone-dependent breast cancer.

Binding, Competitive↗
PubMed1993

[Phase II study of NK 622 (toremifene citrate) in advanced breast cancer, a multicentral cooperative dose finding study].

In order to determine the usual dose in the first line therapy and a high dose in the second or third line therapy, a dose finding study of a novel antiestrogen NK 622 (toremifene citrate) was performed in patients (pts) with advanced or recurrent breast cancer. NK 622 was orally administered daily once for more than 8 weeks. In pts without previous drug therapy or in pts with cancer relapse after adjuvant therapy, the response rates [(CR + PR)/total] were 24.1% (7/29), 13.8% (4/29), 20.0% (1/5) and 40.0% (2/5) at doses of 40, 60, 120 and 240 mg/day, respectively. A 40 mg/day dose showed an objective response only in postmenopausal pts with estrogen receptor (ER) positive or unknown cancer. At a dose of 60 mg/day, some of the responding cases were premenopausal pts or pts with ER(-) cancer. In pts with cancer relapse during adjuvant therapy or in those with previous therapy and/or radiation, response rates were 25.0% (2/8), 0% (0/4), 13.5% (5/37) and 10.3% (4/39) at doses of 40, 60, 120 and 240 mg/day, respectively. Response was more frequent in pts with ER (+) cancer than with ER (-) cancer. The response rates in pts with previous therapy including tamoxifen (TAM) except medroxyprogesterone (MPA) were 14.3% (4/28) at a 120 mg/day dose and 6.1% (2/33) at a 240 mg/day dose. In pts with previous therapy including TAM, MPA and other antitumor agents, the rate was 18.2% (2/11) at a 120 mg/day dose. Side effects such as elevation of GOT, GPT and serum Ca level, decrease of hemoglobin, anorexia, nausea/vomiting, fatigue, dizziness and hot flush were observed. These side effects were moderate in grade and reversible. Dose dependency of side effects was not clearly observed in grade and incidence. From these results, NK 622 is expected to be a safe drug with efficacy in first line therapy at a dose of 40 mg/day and in second or third line therapy at a dose of 120 mg/day.

Administration, Oral↗
PubMedDate not supplied

The effect of ICI 164384 and beta-interferon on the growth and steroid receptor profile of breast cancer cell lines.

We investigated the effect of a concomitant treatment of ICI 164384 and B-interferon (beta-IFN) on the growth of estrogen-receptor-positive (ER+) and estrogen-receptor-negative (ER-) breast cancer cell lines and on their steroid receptor profiles. ICI 164384 reduced cell proliferation not only in ER+ but also in ER- cell lines and completely suppressed the stimulation induced by estradiol (E2) in hormone-sensitive cell lines, MCF7 and T47D. When associated with beta-IFN, ICI 164384 increased the inhibitory effect exerted by the low concentration of beta-IFN. Moreover, ICI 164384, singly or in association with beta-IFN, did not affect ER and PgR concentration in ER- cell lines, whereas in ER+ cell lines we observed an almost total disappearance of ER and PgR. In conclusion, our study seems to indicate that, although beta-IFN is able to control the proliferation of hormone-sensitive and hormone-independent subclones, it does not further improve the antiproliferative activity of ICI 164384. In contrast, the presence of ICI 164384, which does not induce the selection of resistant subclones under the same experimental conditions in which TAM does, may improve the efficacy of low concentration of beta-IFN and prevent the development of a secondary TAM-induced resistance.

Adenocarcinoma↗
PubMed1996

[Chemo-/immunotherapy in advanced malignant melanoma: carboplatin and DTIC or cisplatin, dtic, bcnu and tamoxifen followed by immunotherapy with interleukin 2 and interferon alpha-2a].

BACKGROUND: Polychemotherapy and immunomodulating treatment using IL-2 and/or IFN-alpha produce objective responses in a proportion of advanced malignant melanoma patients. PATIENTS AND METHODS: In 2 consecutive phase II trials in a total of 85 patients, we assessed the potential synergism between both modalities i.e., chemo- and immunotherapy. Treatment consisted of intravenous carboplatin (CBDCA, 400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice at a 3-week interval, or 4 cycles of DTIC (220 mg/m2 i.v. x 3 days), cisplatin (DDP 35 mg/m2 i.v. x 3 days), carmustine (BCNU 150 mg/m2 i.v., cycles 1 and 3) and tamoxifen (TAM 20 mg/per os x 5 days) at a 3-week interval. Chemotherapy was followed by immunotherapy with combined subcutaneous interleukin-2 and (rIL-2) and s.c. interferon-alpha 2a (rIFN-alpha). RESULTS: Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CR) with durations of 13 to 26+ months. Partial remissions (PR) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5 to 14) months. Among 45 patients who received DTIC/DDC/DDP/BCNU and TAM and sequential rIL-2/rIFN-alpha 2a there were 5 (11%) complete remissions and 17 (38%) partial remissions. Duration of complete and partial remissions ranged from 8+ to 24+ months (median 12+) and 5+ to 17 months (median 8+), respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 17 days following start of the chemotherapy. 19 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side-effects; malaise, fever, chills, nausea/vomiting, diarrhea, anorexia and arthralgias were most frequent (70% to 100%), but spontaneously reversible after ending the immunotherapy. A mean of 87% (trial I) to 89% (trial II) of the projected doses of rIL-2 and rIFN-alpha were administered on either protocol. There were no life-threatening complications and no treatment-related deaths. CONCLUSION: The sequential combination of chemotherapy and immunotherapy had at least additive therapeutic activity against metastatic malignant melanoma. Both schedules produced long-lasting remissions and were overall well tolerated. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.

Adult↗
PubMed1995

Cytokine regulation of monocyte recruitment.

Phagocytes infiltrating neoplastic tissues have peculiar membrane phenotype and functional properties. Tumor-associated macrophages (TAM) play a complex, ambiguous role in the regulation of primary tumor growth and metastasis (a "macrophage balance"). Yet these cells are strategically located at the very interface between tumor and host and represent a potential target for immunomodulation. A better understanding of the regulation and function of TAM may provide a less empirical basis of or rational design of therapeutic approaches, as vividly illustrated by the antitumor activity of i.p. in IFN ovarian cancer patients with minimal residual disease resistant to chemotherapy.

Animals↗