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Biomedical subjects

E Petru

Publications and source records attributed to E Petru.

At least 91 records · Page 5Linked to original sources
PubMed1989

Long-term carcinogenicity of cyclophosphamide in two mouse strains with different spontaneous leukemia incidence.

The aim of the present study was to investigate to what extent the induction of leukemia by the carcinogenic agent cyclophosphamide (CPA) might be influenced by the genetic predisposition. CPA was s.c. administered at 26 mg/kg and 13 mg/kg weekly for lifetime to AKR mice which are genetically predisposed to develop leukemias, and to NMRI mice, that exhibit a low spontaneous leukemia rate. CPA dose-dependently increased the median life span in AKR mice by 27% and 76% (P less than 0.001), and decreased the incidence in leukemias by 17% and 37% (P less than 0.01), respectively. In NMRI mice, CPA significantly increased the incidence of leukemias by 46% at the low dose (P less than 0.02) and 26% at the high dose (P less than 0.03), respectively. The apparently parallel observations of the lower leukemia incidences following the higher CPA-dosage in both strains probably are related to different mechanisms of action: in the susceptible, genetically determined AKR mice the therapeutic effect of CPA prevailed its carcinogenic potential and the genetic host factors whereas in the resistant NMRI mice the cytotoxic efficacy of CPA reduced its carcinogenicity at the higher dosage.

Animals↗
PubMed1989

Prognostic implications of residual tumour volume in stage III ovarian cancer patients undergoing adjuvant cytotoxic chemotherapy.

Despite recent improvements, the survival of patients with advanced ovarian cancer remains unsatisfactory. In our patients who underwent radical debulking surgery, including systematic pelvic (and, additionally, in about one-third, para-aortic lymphadenectomy), the size of residual tumour volume prior to cytotoxic chemotherapy was the most critical single prognostic determinant. The value of complete tumour removal was reflected in the survival curves. Patients with no residual disease following debulking surgery who underwent complete adjuvant chemotherapy showed a significantly better survival than did women with residual tumour burdens (P less than 0.05). The actuarial 1-year survival rate in patients with no RD, RD less than 2 cm, and RD greater than 2 cm was 96%, 88%, and 83%, the 3-year survival rate was 78%, 56%, and 37%, and the 5-year survival rate was 78%, 40%, and 21%, respectively. Our results agree with previous studies. The data underline the need for aggressive debulking, including systematic lymphadenectomy and subsequent chemotherapy. The smaller the initial cell population the smaller the probability of drug-induced resistance. The greater the diameter of a tumour the greater the number of cells which remain in the G0 phase--and which are thus not susceptible to chemotherapeutic compounds.

Adult↗
PubMed1989

[The obstetric risk in adolescent primiparous females].

The obstetric risks in primiparae between 12 and 17 years of age have been reviewed in cases treated at our hospital from 1982 to 1987. We looked for intrauterine foetal deaths, premature deliveries (birth weight less than 2500 g), breech presentations, preeclampsia, Caesarean sectio rate, forceps rate, and thirdstage complications. The risks found in the group of 476 young primiparae were compared to those amongst the 26,768 overall deliveries during the same period. The incidence of breech presentations, preterm deliveries and forceps deliveries was about the same as in the general group. Intrauterine foetal death, thirdstage complications, Caesarean section deliveries, and, especially preeclampsia, were (markedly) less common than in the overall group. As a result, we no longer consider youthful mothers from our area a higher obstetric risk.

Adolescent↗
PubMed1989

[Are there pre- or perinatal risk factors for sudden infant death?].

The question was posed, whether a relationship could be established between prenatal and perinatal events and subsequent sudden infant death. The birth records of eighty mothers, whose infants died of sudden infant death syndrome (SIDS) between 1982 and 1987, were reviewed for obstetric complications. The records immediately following the respective SIDS cases served as controls. A family history of SIDS was found significantly more often in the SIDS group than in the control group (p less than 0.001). Oxytocin was administered significantly more often in the SIDS group than in the control group: 54/80 (= 68%) and 20/80 (= 25%, p less than 0.001), respectively. Smoking, hypotension requiring treatment and the administration of tocolytic agents were found significantly more frequently in the SIDS group than in the control group (p less than 0.01, p less than 0.001, and p less than 0.05). Transient fetal hypoxia, as a result of reduced flow in the uterine artery, seems possibly to be connected to the vasoactive agent Oxytocin when occurring in the three above named groups. Whether these situations are connected to a later development of SIDS, has not, to date, been confirmed.

Birth Weight↗
PubMed1989

Efficacy of adjuvant carboplatin-epirubicin chemotherapy in advanced ovarian cancer after radical surgery.

Postoperatively, 13 patients with stage III ovarian cancer received a combination of carboplatin and epirubicin (PE) at 300 and 60 mg/m2 respectively. The results of the 13 patients receiving the PE regimen were retrospectively compared to those of 24 patients who received the conventional PAC schedule (cisplatin, Adriamycin and cyclophosphamide at a dosage of 50, 50 and 750 mg/m2, respectively). All 37 patients had undergone radical debulking surgery including pelvic and paraaortic lymphadenectomy. At 8 months, relapse-free rates of 42.2 and 79.2% were observed in the PE and PAC groups, respectively. This difference was highly significant (p = 0.011). The data suggest that the PE combination has less antineoplastic activity than the PAC schedule and thus cannot be recommended in the adjuvant treatment of advanced ovarian cancer.

Adult↗
PubMed1989

Cytostatic activity of an estradiol-linked nitrosourea in MXT mammary carcinoma and L 5222 leukemia.

Investigation of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol-17-ester (CNC-ala-17-E2) and of the unlinked single agents 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine (CNC-ala) and estradiol in the MXT mammary carcinoma in vivo uncovered a significant antitumor activity only for CNC-ala-17-E2 at a non-toxic dose level (growth inhibition greater than 70%). In vitro investigations using the clonogenic assay had a comparable result: Here, too, CNC-ala-17-E2 was superior to the unlinked single agents. No difference in therapeutic activity between CNC-ala-17-E2 and CNC-ala could be observed in a transplanted rat leukemia (L 5222).

Animals↗
PubMed1988

Comparison of in vivo and in vitro activity of estrogen-linked nitrosoureas in methylnitrosourea-induced rat mammary carcinoma.

The anticancer activity of estradiol-linked 2-chloroethylnitrosoureas in methylnitrosourea-induced rat mammary carcinoma was investigated using the short-term assay and the bilayer soft agar system after in vitro exposure as well as the monolayer methylcellulose assay following in vivo treatment. The aim was to evaluate to what extent previous in vivo findings are paralleled by the results of two in vitro test systems and the monolayer culture technique ex vivo. From the test systems investigated and under the conditions used, the results of the short-term test and the monolayer methylcellulose assay did not show a correlation with previous in vivo findings. Only the results of the bilayer clonogenic assay paralleled therapeutic parameters in vivo, although the degree of activity obtained in vivo was not reflected in vitro.

Animals↗
PubMed1988

No relevant influence on overall survival time in patients with metastatic breast cancer undergoing combination chemotherapy.

The results of clinical studies dealing with first and second line chemotherapy of metastatic breast cancer published between 1975 and early 1986 which involved 9350 women were reviewed. Our special aim was to evaluate combination chemotherapy and its influence on overall survival in late stage breast cancer patients. No significant improvement in overall survival times was found in this selected group of patients who were treated with intense palliative chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

In vitro evaluation of an estradiol-linked nitrosourea in mammary carcinomas of mouse, rat and man.

In vitro activity of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol-17-ester (CNC-ala-17-E2) at three concentrations in transplanted MXT mammary carcinoma in B6D2F1 mice and autochthonous methylnitrosourea (MNU)-induced mammary carcinoma in Sprague-Dawley rats, as well as in 30 human primary breast carcinomas using the bilayer soft agar assay is described. Eighty-five per cent of MXT tumors showed a more than 70% inhibition of colony formation following CNC-ala-17-E2. In the MNU-induced model this high degree of inhibition was not observed: only 5% of individual tumors showed an inhibition up to 70%, but a superiority of the hormone-linked agent over the unlinked single agents was nevertheless discernible. In contrast, in human breast carcinomas a response at this sensitivity level could not be assessed. Thus, in the MXT mammary carcinoma the in vitro results paralleled previous findings in vivo, whereas in the MNU-induced autochthonous tumor model this close in vivo-in vitro correlation was not observed. The discrepancy between in vivo and in vitro results found in the autochthonous rat model indicates that hormone-linked nitrosoureas should not necessarily be abandoned for the treatment of human breast carcinoma on the basis of negative in vitro results alone.

Adult↗
PubMed1988

Pelvic and para-aortic lymphadenectomy in cervical cancer.

The surgical treatment of invasive cervical cancer must both remove the primary tumour and eliminate the paths by which it spreads--i.e., the lymphatics and the lymph nodes. In 359 patients, systematic pelvic lymphadenectomy yielded positive nodes in 30.3% of Stage Ib and in 44.7% of Stage IIb cases. In the 140 patients with positive nodes, the obturator group was involved in 76.4%, the external iliac group in 62.8%, and the presacral and subaortic nodes in only 4.3%. One node group was involved in 55% of the patients, two and three groups in 27.8% and 7.1% respectively. In patients with only one positive node group, the obturator nodes were involved the most often (31.4%), followed by the external iliac (21.4%) and parametrial nodes (9.2%). Nine patients with Stage Ib and 31 patients with Stage IIb disease underwent para-aortic as well as pelvic lymphadenectomy. Positive para-aortic nodes were found in 11.1% and 22.6%, respectively; 12.5% of these patients had major complications, but there was no surgical mortality. Since radiotherapy cannot sterilize positive nodes, systematic pelvic and para-aortic lymphadenectomy may improve the survival of such patients.

Aorta↗
PubMed1988

Carcinogenicity of 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3- nitrosoureahydrochloride and three related N-nitroso derivatives following repeated intravenous administration to male Wistar rats.

Long-term toxic evaluation of 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3- (2-chloroethyl)-3-nitrosoureahydrochloride (ACNU), 1-(2-chloroethyl)-1-nitroso-3-(methylene-2-pyridylium)-urea- hydrochloride (CNMPU), 1-(2-chloroethyl)-1-nitroso-3-(4-thiomorpholino)-urea (CNTMU) and 4-[N-(2-chloroethyl)-N-nitrosocarbamoyl]-morpholine (CNCM) which were administered each at five dosages, adapted to the clinical situation, revealed significantly increased tumor risks for the first three agents in the lung and the adrenal gland. Additionally, CNTMU and ACNU induced a significant rise in the tumor load of the neurogenic tissue; the latter compound, being in clinical use, was associated with a significantly increased number of mammary tumors as well. CNCM, however, did not exhibit significantly elevated carcinogenic activity, although the overall tumor load was up to 2.4-fold increased compared to controls. The results indicate no advantage of the newly developed ACNU with respect to its inherent carcinogenic risk as compared to clinically established 2-chloroethyl-N-nitroso derivatives.

Animals↗
PubMed1988

[Chemotherapeutic characterization of new nitrosourea compounds].

The development of new nitrosoureas is described using selected examples. Results obtained with water-soluble analogs and with compounds linked to biomolecules as for instance amino acids, oligopeptides and steroids, are presented. The pronounced antineoplastic effect of some water-soluble analogs is paralleled by an increased rate of DNA-interstrand cross-links and by an increased suppression of hematopoietic stem cells. The suppression of bone marrow stem cells is followed by their rapid regeneration. Water-soluble nitrosoureas induce significant less inhibition of glutathione reductase as compared with established compounds. With regard to long-term toxicity and carcinogenicity water-soluble are superior to established compounds as for instance BCNU. Linking of the nitrosourea moiety to amino acids and oligopeptides led to some analogs with outstanding therapeutic ratio. Out of a group of steroid-linked nitrosoureas, CNC-L-alanine-estradiol-17-ester (CNC-ala-17-E2) is chosen to demonstrate the possibility of reducing bone marrow toxicity despite unchanged or increased therapeutic activity by attachment of the nitrosourea moiety to a steroid. Results of a comparative interspecies in vitro evaluation of CNC-ala-17-E2 in transplanted MXT mammary carcinoma of the mouse, MNU-induced autochthonous rat mammary carcinoma and primary human mammary carcinomas are presented and the question is discussed to what extent in vitro activity of such receptor agents using the tumor stem cell assay reflects their in vivo activity.

Animals↗
PubMed1987

On the role of additive hormone monotherapy with tamoxifen, medroxyprogesterone acetate and aminoglutethimide, in advanced breast cancer.

We analyzed the results of clinical studies on the therapeutic efficacy of hormone monotherapy with tamoxifen, medroxyprogesterone acetate, and aminoglutethimide in metastatic breast cancer, which were published between 1971 and 1986 and involved altogether 7000 patients. The overall response rates in patients treated with these hormonal single agents at various dose levels ranged from 31%-42%. When only estrogen receptor-positive patients were considered, the response rates lay between 41% and 54% in groups which were treated with the antiestrogenic agents tamoxifen or aminoglutethimide. The duration of remission was 12 months for tamoxifen- and aminoglutethimide-treated women, whereas medroxyprogesterone acetate effected remissions lasting from 6-16 months. The overall mean survival from start of therapy in tamoxifen- and aminoglutethimide-treated groups was 20 months, whereas information concerning this therapeutic parameter was available only in a minority of medroxyprogesterone acetate-treated groups. With respect to the response by site of metastatic lesions, all three agents caused a significantly higher degree of remissions in the soft tissue as compared to visceral disease.

Aminoglutethimide↗