Side of origin of ovarian cancer.
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Female↗
Biomedical subjects
G Bolis
Publications and source records attributed to G Bolis.
Potentials of cell kinetics in the management of patients with ovarian cancers.
The relevance of 3H-thymidine labeling index (3H-dt LI) on clinical outcome was evaluated on 85 patients with advanced ovarian cancers treated with carboplatin or cisplatin alone (39 cases) or cisplatin in association with doxorubicin and/or cyclophosphamide (46 cases). 3H-dT LI of the primary tumour was significantly related to the 3-year probability of survival in patients treated by monochemotherapy (low LI, 63%; high LI, 21%; P = 0.013) but not in those treated with polychemotherapy. Analysis of the relation between cell kinetics and clinical outcome as a function of treatment showed that in patients with rapidly proliferating tumours the 3-year survival was significantly higher following polychemotherapy than monochemotherapy (51 vs. 21%; P = 0.04). In patients with slowly proliferating tumours no significant difference in survival was observed following the two types of treatment for the overall series, whereas in patients not achieving a complete response survival was significantly higher following monochemotherapy than polychemotherapy (61 vs. 9%; P = 0.008).
Antineoplastic Combined Chemotherapy Protocols↗
Laparoscopic aspiration of ovarian endometriomas. Effect with postoperative gonadotropin releasing hormone agonist treatment.
In the period 1988-1990 this prospective study of 33 women with moderate or severe endometriosis who underwent laparoscopy for infertility and/or chronic pelvic pain, was conducted to evaluate the efficacy of aspirating endometriotic cysts followed by administration of a gonadotropin releasing hormone (GnRH) agonist in reducing the size of ovarian endometriomas. The cysts (mean diameter, 4.5 cm; range, 2-7; unilateral, 21 cases; bilateral, 12 cases) were punctured, aspirated, washed and emptied completely. After laparoscopy, 15 subjects received goserelin administered as a 28-day subcutaneous depot for three months, whereas 18 patients undergoing simple observation constituted internal controls. Ultrasound scans were performed before and at one, three and six months after laparoscopy. One case and three controls requested surgery between the four- and five-month follow-up scans and did not complete the study. All the other women had recurrent cysts at the six-month scan. There were no significant differences in mean endometrioma diameter between the two groups at any observation time nor between prelaparoscopic and six-month ultrasound examinations within each treatment group. We conclude that aspiration and washing of endometriotic cysts, combined with postoperative administration of GnRH agonists or not, is ineffective.
Adult↗
A machine learning approach to computer-aided molecular design.
Preliminary results of a machine learning application concerning computer-aided molecular design applied to drug discovery are presented. The artificial intelligence techniques of machine learning use a sample of active and inactive compounds, which is viewed as a set of positive and negative examples, to allow the induction of a molecular model characterizing the interaction between the compounds and a target molecule. The algorithm is based on a twofold phase. In the first one--the specialization step--the program identifies a number of active/inactive pairs of compounds which appear to be the most useful in order to make the learning process as effective as possible and generates a dictionary of molecular fragments, deemed to be responsible for the activity of the compounds. In the second phase--the generalization step--the fragments thus generated are combined and generalized in order to select the most plausible hypothesis with respect to the sample of compounds. A knowledge base concerning physical and chemical properties is utilized during the inductive process.
Amino Acid Sequence↗
Salvage chemotherapy for ovarian cancer recurrence: weekly cisplatin in combination with epirubicin or etoposide.
From December 1986 to April 1990, 40 consecutive ovarian cancer patients who relapsed after response to cisplatin-based chemotherapy regimens were treated with seven courses of weekly cisplatin, in combination with epirubicin or etoposide. The overall response rate obtained with the intensive schedule was 60% and the complete response rate was 25%; median duration of response was 7 months and median survival time, 13.5 months. Responsive cases seem to have longer survival; a prognostic factor for response to salvage treatment and longer survival is the disease-free interval after the first-line chemotherapy. Weekly cisplatin as intensive treatment was very well tolerated and showed acceptable toxicity in both the combination protocols with epirubicin or etoposide.
Adult↗
Randomized comparison of hexamethylmelamine, adriamycin, cyclophosphamide (HAC) vs. cisplatin, adriamycin, cyclophosphamide (PAC) in advanced ovarian cancer: long-term results.
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Altretamine↗
The impact of whole-abdomen radiotherapy on survival in advanced ovarian cancer patients with minimal residual disease after chemotherapy.
Between March 1982 and March 1987, 26 patients with minimal residual epithelial ovarian cancer after cisplatin-based chemotherapy were treated with whole-abdomen irradiation [moving-strip technique (MST)] with or without pelvic boost. Prior to radiation residual disease was macroscopic (less than or equal to 0.5 cm) in 8 cases and microscopic (positive random biopsies) in 18 cases (8 diffuse, 10 localized). Eighty percent of patients completed the planned therapy, 34% with interruptions secondary to hematologic or gastrointestinal toxicity. With a median follow-up time from completion of radiotherapy of 24 months, 34.6% of patients remain alive. The 3-year survival rates (from the second-look procedure) are 50% for the patients with microscopic tumor and 25% for those with macroscopic residual disease. Progression-free intervals are statistically different in the two groups: 16.9 months for microscopic residuals and 6.16 months for macroscopic tumors (P = 0.037). All but two of the recurrences were in the irradiated field (pelvis and/or abdomen); one was distant (pleural) and one only retroperitoneal. Small bowel injury was the most limiting complication: 3.8% was registered as fatal acute enteritis and 19% as late obstruction or malabsorption syndrome, necessitating surgical intervention in 10% of treated cases.
Biopsy↗
Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).
The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed.
Age Factors↗
Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin.
The aim of this multicenter randomized trial was to compare carboplatin (400 mg/m2) and cisplatin (100 mg/m2) in patients with untreated advanced epithelial ovarian cancer. Toxicity and treatment efficacy assessed by pathological response rate, progression-free survival, and survival were the endpoints of the study. One hundred seventy-three patients with advanced epithelial ovarian cancer, F.I.G.O. (International Federation of Gynecology and Obstetrics) stage III and IV were accrued in the trial. The median follow-up time was 15 months (maximum, 34); three patients in each treatment arm were not eligible (four, nonepithelial ovarian cancer type; one, no data, and one, stage II). Patient characteristics were similar in the two groups. In the carboplatin-treatment arm, the overall pathological response rate was 57.3% and the complete pathological response rate was 26.8%. In the cisplatin-treatment arm, the overall pathological response rate was 71.6% and the complete pathological response rate was 24.7%. There was no statistical difference in the two arms in survival or progression-free survival. Cisplatin was more nephrotoxic while carboplatin induced a higher degree of myelosuppression, especially thrombocytopenia; however, severe hematological toxicity was seldom observed. Carboplatin is a cisplatin analog with definite activity in ovarian cancer, but it is more active than the parent compound. Because of less nonhematological toxicity, carboplatin is undoubtedly a useful substitute in patients who cannot be given cisplatin. Further experience is needed to indicate whether or not carboplatin should completely displace cisplatin in the clinical treatment of ovarian cancer.
Adult↗
CA 125 reliability in predicting ovarian cancer recurrence.
The predictive value of CA 125 assay for recurrence in ovarian cancer patients in follow-up was analyzed in a study from April 1984 through June 1987. Forty-two patients with no evidence of disease (NED), with positive antigen levels at diagnosis and negative at the end of active treatment, were considered eligible for the analysis. Median follow-up time was 16 months (range, 5-34). Outcome analysis revealed 19 cases still NED: 16 had normal CA 125 levels (less than 35 U/ml). The 3 patients with positive antigen titers were intensively investigated with no evidence of recurrence. Twenty-three cases had disease recurrence: 13 of them had elevated marker levels prior to relapse diagnosis, with a median lead time of 5 months (range, 2-13). In contrast, 10 patients had positive titers at or soon after the recurrence. Test sensitivity was therefore 56% and specificity 84%. Predictive value for recurrence of elevated CA 125 levels was 0.81.
Adult↗
Cell kinetics: a prognostic marker in epithelial ovarian cancer.
The proliferative activities (3H-thymidine labeling index, LI) of 72 primary ovarian cancers and 76 metastatic lesions from untreated patients were evaluated. Overall, median LI values for primary and metastatic lesions were similar (7.8 vs 7.0%), but cell kinetics significantly differed in metastases from different sites. The LI of the primary tumor was unrelated to pathologic stage and histology, but was significantly correlated with histologic grading (P = .014). The prognostic relevance of LI was assessed for 43 untreated patients at stage III-IV (90% with bulky residual disease), treated after staging laparatomy with five cycles of cisplatin or of carboplatin. For 19 patients the LI was determined for both primary tumor and metastases, for 15 for the primary, and for 12 for the metastatic lesions. Complete remission (CR) was unrelated to pretreatment LI, although a trend toward a higher rate of CR was observed with rapidly proliferating tumors. Patients with slowly proliferating primary tumors had a higher probability of 1.5-year survival than patients with rapidly proliferating tumors (83 vs 50%). The difference was even greater between patients with both primary and metastatic lesions proliferating slowly (100%) and patients with at least one (61%) or both lesions proliferating rapidly (60%). Pretreatment LI was not predictive for survival in subgroups of patients who attained CR, but it was quite predictive for survival in patients responding only partially or not at all (90 vs 32%, P = .025).
Antineoplastic Agents↗
Drug sensitivity of different tumor lesions from the same patient evaluated by a short-term assay.
A short-term antimetabolic assay, which considers the interference with [3H]thymidine incorporation as an indicator of drug effect, has been used to comparatively assess the chemosensitivity of different tumor lesions from the same patient. The analysis was performed on primary tumors and their synchronous metastases from 67 patients with breast, ovarian, gastrointestinal and germ cell testicular tumors. A remarkable difference in sensitivity to cytostatic drugs was observed between the two lesions. In contrast, a strong association in chemosensitivity (81.7% agreement rate; p less than 0.01) was observed between two synchronous metastases from 17 patients with breast, ovarian, germ cell testicular tumors or malignant melanoma. In addition, the predictive relevance of the antimetabolic assay on clinical response to chemotherapy was analyzed in relation to the type of tumor lesion tested in vitro in a retrospective correlative study on 57 patients with advanced ovarian and germ cell testicular tumors. The objective clinical response was significantly correlated to the in vitro sensitivity of metastases (83.7% agreement rate; p less than 0.01), but not to that of the primary tumor.
Antineoplastic Agents↗
Analysis of 309 cases after hydatidiform mole: different follow-up program according to biologic behavior.
Between 1976 and 1985, at the Obstetrics and Gynecology Department of Milan University, a total of 309 cases of hydatidiform mole, 223 complete moles and 86 partial moles, were monitored with the assay of beta-human chorionic gonadotropin, following a postmolar biochemical surveillance program. Spontaneous remission of the disease occurred in 287 (92.9%) patients. Marker levels were undetectable in 80.4% of cases within 60 days after evacuation of the mole and in 19.6% between 61 and 140 days. There were 22 (7.1%) patients diagnosed as having gestational trophoblastic tumors (GTT) and treated with chemotherapy: 20 were complete moles and 2 partial moles. Considering these data, the authors suggest different follow-up times for partial and complete moles and confirm the necessity of selection criteria in a diagnosis of GTT.
Choriocarcinoma↗
EMA/CO regimen in high-risk gestational trophoblastic tumor (GTT).
From June 1980 through December 1985, 36 high-risk GTT patients received Bagshawe's EMA/CO regimen, 22 as first-line, and 14 as second-line treatment, after primary chemotherapy with CHAMOCA, or cyclic regimen, or MTX-CF. All treated patients were metastatic at the start of treatment with EMA/CO; three showed liver metastases and one brain metastasis. Seventeen patients had a high score, greater than 15. Nineteen patients had histologically confirmed diagnosis of choriocarcinoma. The overall response rate was 86% with 81% survival during a median observation time of 32 months. The median number of courses needed to achieve complete remission was 3 (range 3-7). Toxicity was acceptable, and was less than with CHAMOCA and MAC regimens. Only 1 out of 17 high-risk patients developed drug resistance, and 3 needed urgent surgery. The relapse rate of responders was 19% after a median of 5.5 months. The survival rate of high-risk patients was 88%, of which 76% are alive with no evidence of disease, while 12% have still detectable beta-chorionic gonadotrophin. The remission rate in the second-line treatment group was 64%, higher than using other regimens such as MAC or CHAMOCA. In conclusion, we consider EMA/CO to be the best choice for patients with high-risk GTT, because it is effective and well tolerated. In our opinion, the cure rate of high-risk GTT could perhaps be improved by starting trials to establish what salvage treatment to employ after EMA/CO failure and using more aggressive first-line chemotherapy in selected high-risk patients, on the basis of the scoring system.
Adult↗
Renin inhibitors. Dipeptide analogues of angiotensinogen utilizing a structurally modified phenylalanine residue to impart proteolytic stability.
A series of renin inhibitors have been prepared and evaluated for their susceptibility to cleavage by the serine protease chymotrypsin. The compounds were designed by consideration of the structural requirements in the active-site region of renin and chymotrypsin. By systematic alteration of the P3 phenylalanine residue, compounds with varying degrees of renin inhibitory potency and chymotrypsin susceptibility were obtained. Selected analogues from this group were examined in vivo for both their hypotensive effects and metabolic patterns.
Angiotensinogen↗
Renin inhibitors. Design and synthesis of a new class of conformationally restricted analogues of angiotensinogen.
Molecular modeling methods have been used to design a novel series of conformationally constrained cyclic peptide inhibitors of human renin. Three goals were defined: enhanced inhibitory potency, high specificity for renin, and increased metabolic stability. Three cyclic compounds were synthesized with ring sizes 10, 12, and 14, based upon a linear hexapeptide inhibitor with a reduced amide replacing the scissile bond at the active site. When tested, the 14-membered-ring compound was as potent an inhibitor of human renin as the parent while the 12-membered-ring compound was 6-fold more potent than the parent against mouse renin. However, the 10-membered-ring compound was inactive against both renins. The lack of potency of the 10-membered compound was explained by using NMR and molecular modeling techniques. It forms another conformation in solution that is inconsistent with binding at the active site. The cyclic compounds did not inhibit either pepsin or cathepsin D significantly. The cyclic modification rendered these inhibitors significantly resistant to cleavage by chymotrypsin and thus prevented loss of activity by this enzyme. Thus, the goals of enhanced inhibitory potency, high specificity, and metabolic stability were achieved in the series of compounds.
Angiotensinogen↗
New inhibitors of human renin that contain novel Leu-Val replacements. Examination of the P1 site.
Stereoselective syntheses of several nonpeptide sulfidoethanol fragments that function as Leu10-Val11 (P1-P1') scissile bond replacements in human angiotensinogen are presented. These fragments are prepared from a variety of amino acids with formal P1 side chains varying in size and lipophilicity by converting them to their corresponding N-protected aminoalkyl epoxide 5 followed by ring opening with isopropyl mercaptan. The coupling of these fragments to either Boc-Phe-Ala-OH or Boc-Phe-His-OH produces inhibitors of human renin, 6 and 7, respectively, which are compared to a series of dipeptide-aldehyde inhibitors, 4, by molecular modeling and biochemical methods. Qualitatively, histidine-containing (P2) inhibitors 7 possess greater inhibitory potency than their corresponding alanine (P2) analogues 6, which are more potent than the corresponding aldehydic inhibitors from series 4. Within a given series, inhibitors with the cyclohexylmethyl P1 side chain are more potent than the benzyl analogues, which in turn are more potent than cyclohexyl or isobutyl derivatives. Inhibitors with parger P1 side chains (e.g. adamantylmethyl and benzhydryl) are much less active. The inhibitory potency of these compounds against human renin is discussed in terms of specific interactions with the enzyme.
Amino Acid Sequence↗
Methotrexate with citrovorum factor in low-risk gestational trophoblastic tumor.
From January 1976 through December 1985, methotrexate (MTX) with citrovorum factor (CF) was administered as primary treatment to 57 patients with low-risk gestational trophoblastic tumor (GTT); 51 patients were non-metastatic and 6 were metastatic GTT. The median number of courses needed to achieve biochemical remission was two (range, 1-7). Complete remission was attained in 95% of non-metastatic GTT patients with postmolar persistent trophoblastic disease, but when choriocarcinoma was histologically confirmed, this fell to 60%. The cure rate of metastatic GTT patients was only 50%. The overall remission rate with the MTX-CF combination was 84.2%. Toxicity was mild, consisting of myelosuppression and mucositis. Fifteen patients were resistant to MTX-CF, or relapsed subsequently, but they all achieved remission with chemotherapy rescue treatment (VP 16 alone, EMA/CO, CHAMOCA). Two patients required a pulmonary lobectomy. They are all still alive in biochemical remission with a median survival of 54 months. Our experience suggests that drug resistance and relapse rate seem related to a beta-HCG value higher than 10(4), an enlarged uterus with myometrial deep involvement, and a histologically confirmed diagnosis of choriocarcinoma. In conclusion, the MTX-CF combination is effective in postmolar GTT, whereas a different therapeutic approach may be considered for a "special" low-risk group of patients, on the basis of prognostic factors.
Female↗