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Biomedical subjects

G Bolis

Publications and source records attributed to G Bolis.

At least 91 records · Page 5Linked to original sources
PubMed1987

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↗
PubMed1987

Structure refinement of a cyclic peptide from two-dimensional NMR data and molecular modeling.

The conformational and dynamic properties of a cyclic peptide designed to inhibit human renin have been examined by using NMR and molecular modeling. From a quantitative analysis of a series of two-dimensional NOE data sets, proton-proton distances were calculated. Several different methods were explored and compared to incorporate these distance constraints as well as those derived from vicinal spin-spin coupling constants into computer-generated three-dimensional structures. These methods included interactive manual manipulation of the structures to fit the NMR-determined distance constraints, distance geometry, constrained energy minimizations, and constrained molecular dynamics. The advantages and disadvantages of the methods are discussed. In addition, to gain insight into the conformations accessible to the cyclic peptide and the relative flexibility of the different parts of the molecule, molecular dynamics calculations were performed at three different temperatures. Average interproton distances and dihedral angles were obtained from the structures generated in the dynamics trajectories and compared to those obtained from the NMR experiments. Despite the four methylene groups and ether linkage contained in the cyclic portion of the peptide, our NMR results indicated a preferred conformation for the macrocyclic ring of the peptide and supported the presence of a cis Phe-Ala peptide bond. In contrast, both the molecular dynamics and NMR data indicated a considerable amount of flexibility for the remaining noncyclic portion of the molecule. These results are used to propose an explanation for the cyclic peptide's inability to inhibit human renin.

Algorithms↗
PubMed1987

Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma.

Serum CA 125 was measured in 100 patients with ovarian epithelial carcinoma at diagnosis and in follow-up. Levels over 35 U/ml were found in 43 (75.4%) of 57 cases at diagnosis and in 21 (48.8%) of 43 cases in follow-up. A correlation was found between tumor burden and marker positivity: advanced Stages (III and IV) and recurrences had 84.2 and 91% of positivity, compared to 59.1% in early disease (Stages I and II). Analysis by histotype and FIGO grade revealed a difference between the mucinous type and the others and a positive association with less differentiated tumors. In the 30 patients submitted to second-look laparotomy a correlation was found between CA 125 levels and pathological response in 86.7% of cases. This ovarian cancer marker may thus be more useful in monitoring the response to treatment and in long-term follow-up than in diagnosis.

Antigens, Neoplasm↗
PubMed1987

Renin inhibitors. Dipeptide analogues of angiotensinogen incorporating transition-state, nonpeptidic replacements at the scissile bond.

A series of dipeptide analogues of angiotensinogen have been prepared and evaluated for their ability to inhibit the aspartic proteinase renin. The compounds were derived from the renin substrate by replacing the scissile amide bond with a transition-state mimic and by incorporating bioisosteric replacements for the Val-10 amide bond. Analogue 21a exhibited an IC50 of 7.6 nM against purified human renin, showed high specificity for this enzyme, and produced a hypotensive response in anesthetized, salt-depleted cynomolgus monkeys.

Angiotensinogen↗
PubMed1986

Thyroid function in gestational trophoblastic tumors.

Thyroid function was assessed in a total of 15 cases, 7 of whom had choriocarcinoma and 8 hydatidiform mole, by measuring free T3, free T4, thyroxin-binding globulin (TBG), basal thyroid-stimulating hormone (TSH) and after the thyrotropin-releasing hormone test (delta TSH). Free T3, free T4 and TBG were investigated in the same number of healthy women within the first three months of pregnancy. Only 13.4% of the cases presented elevated levels of free T3 and T4 and TBG; TSH and delta TSH were within normal limits. Both thyroid hormones and TBG returned to within normal limits when beta-human chorionic gonadotropin became undetectable. One patient was found to be hypothyroid. Comparison with the control group showed no significant differences except in TBG levels, which were higher in controls. A significant, direct correlation was found between levels of free T3 and T4 and TBG and the pattern of human chorionic gonadotropin.

Adolescent↗
PubMed1986

Frequency of hydatidiform mole in Lombardy, Northern Italy.

The frequency of hydatidiform mole in Lombardy (a region in Northern Italy with 8.9 million inhabitants) over the period 1979-1982 was estimated using the Regional Hospital Discharge Registration System, where information is collected on all discharges from public and private hospitals. After revision of registrations and clinical records, 347 cases of hydatidiform mole were confirmed. The estimated frequency was 66.22 per 100,000 pregnancies (SE = 3.56), or 1 in 1510 pregnancies. The risk of hydatidiform mole was not elevated in teenage women, but rose markedly above age 40, and was almost 300 times higher for women age 50 or older. The frequency of hydatidiform mole observed in the nine provinces of Lombardy was significantly heterogeneous, and this variation could not be explained in terms of differences in maternal age distribution.

Adolescent↗
PubMed1985

The value of endometrial cytology in a high risk population.

Between January 1982 and November 1983, 335 women at risk for endometrial carcinoma, with or without symptoms, were screened on an out-patient basis at the 3rd Department of Obstetrics and Gynecology of the University of Milan for endometrial carcinoma and its precursors. Cytologic diagnosis of material obtained with the Milan-Markley helix (Mi-Mark) was compared, in terms of acceptability and diagnostic accuracy, with histologic diagnosis of material obtained by Vabra curettage. The Mi-Mark was better accepted by the patients and there were almost no complications. Sensitivity was 93% for adenocarcinoma, 62% for atypical hyperplasia and 76% for hyperplasia without atypia. According to epidemiologic data and to our results, we suggest this screening procedure for asymptomatic obese women.

Adult↗
PubMed1985

Potential-derived point-charge model study of electrostatic interaction energies in some hydrogen-bonded systems.

Mulliken's atomic changes (MC) and potential derived (PD) point charges obtained from STO-3G wave functions are used to study the electrostatic interaction energies for a series of representative hydrogen-bonded complexes. The results of the above-mentioned models are compared with the more accurate results of segmental multipole moment (SMM) expansion, and it is shown that the PD model is superior to the MC model. The results of PD model are shown to be well correlated with the results of SMM expansion technique. Results of our calculations using 6-31G and 6-31G** PD charges are also reported here. Electrostatic interaction energies obtained using 6-31G** PD charges are compared with the 6-31G** SCF interaction energies available for the nine hydrogen-bonded dimers of ammonia, water, and hydrogen fluoride and a good correlation between the two is shown. The interrelationship between the results of different basis sets are also examined for the PD point-charge model. The electrostatic interaction energies obtained using STO-3G PD model are shown to be well correlated to the results of 6-31G and 6-31G** PD models.

Ammonia↗
PubMed1985

Hexamethylmelamine, adriamycin, and cyclophosphamide (HAC) versus cis-dichlorodiamineplatinum, adriamycin, and cyclophosphamide (PAC) in advanced ovarian cancer: a randomized clinical trial.

After stratification according to diameter of the largest residual tumor, 120 previously untreated ovarian cancer patients were randomized to receive adriamycin and cyclophosphamide in combination with hexamethylmelamine (HAC) or cis-dichlorodiamineplatinum (PAC). The surgical response rates were 66% to HAC and 70% to PAC, with median times to progression of 14 and 22 months and median survival times of 23 and 24 months, respectively. In patients with residual tumor greater than 2 cm the surgical response rates to HAC and PAC were 56% and 63%, with complete response rates of 13% and 21%, respectively. In two of five complete responders to HAC there has still been no progression at 38 and 48 months, with a median response duration of 25 months. Only one of the nine complete responders to PAC has relapsed, at 33 months, while in the eight others response is maintained at follow-up times of 35-64 months. Myelosuppression was generally mild and similar in the two arms. No significant nonhematological toxicity was reported. It is concluded that at a median follow-up time of 36 months HAC is as effective as PAC in terms of response, duration of remission, and survival in previously untreated advanced ovarian cancer.

Adolescent↗
PubMed1984

Potential-derived point-charge model study of electrostatic interactions in DNA base components.

Ab initio electrostatic potentials obtained using STO-3G wavefunctions for guanine, cytosine, adenine, and thymine are used to calculate potential-derived (PD) point charges for these base components. Calculated PD point charges are used to estimate the electrostatic contributions to hydrogen-bonding and stacking interaction energies of ten sequence isomers of B-DNA. These estimates are in excellent agreement with the results of the more elaborate segmental multipole moment expansion technique.

Adenine↗
PubMed1984

Potential derived point charge model study of electrostatic interaction energies in some complexes of water with uracil, thymine, and cytosine.

Potential derived (PD) point charges and segmental multipole moments are calculated for water, uracil, thymine, and cytosine using STO-3G quality wave functions. The PD point charges are used to estimate the electrostatic interaction energies for a series of complexes of water with these nucleic acid bases. It is shown here that the results obtained using simple PD charge model is very similar to those obtained from more elaborate segmental multipole moment analysis.

Algorithms↗
PubMed1983

The role of surgery in gestational trophoblastic disease.

Fifty-eight consecutive patients with malignant trophoblastic tumors of gestational origin were treated at the 1st Department of Obstetrics and Gynecology of the University of Milan between 1975 and 1981. Thirty-five (60.3%) of the patients were treated with combined surgery and chemotherapy. Of these, 44.8% had genital surgery, 12% extragenital surgery, and 5.1% had emergency laparotomies. Minor surgery was done to 17.1% of the patients. Five patients (20.8%) with tumors limited to the uterus and treated with chemotherapy only became drug-resistant, whereas 3 patients (9%) later developed lung metastases. All the patients are alive without any clinical signs of the disease. When there were metastatic tumors, the survival of the group first submitted to a "debulking" operation of the primary focus was 80%, and the survival of the group treated only with chemotherapy was 78.5%. Seven cases required extragenital surgery for the indications discussed in detail and because they had measurable HCG. Six of these had thoracotomies and one had a craniotomy. Five of the 6 patients who underwent thoracotomy (83.4%) had a complete remission. Chemotherapy remains the treatment of choice for trophoblastic tumors. Nevertheless, our data confirm that for some cases, mostly in the high risk group, complete eradication cannot be obtained with antitumor agents. Adjuvant surgery of carefully selected patients helps to save some of those who no longer respond to chemotherapy.

Adult↗
PubMed1982

Antibody-dependent and -independent cytotoxicity of human mononuclear phagocytes: defective stimulation of tumoricidal activity in milk macrophages.

Human peripheral blood monocytes, milk macrophages and peritoneal exudate macrophages were purified by adherence. antibody-dependent cellular cytotoxicity (ADCC) was measured using the murine TLX9 lymphoma pre-labelled with 3H-thymidine. Direct, antibody-independent tumoricidal activity was measured against the murine TU5 line pre-labelled with 3H-thymidine. All mononuclear phagocyte populations tested were similarly effective in mediating ADCC against TLX9 cells. In the absence of deliberate stimulation blood monocytes and peritoneal macrophages had appreciable spontaneous cytotoxicity against the susceptible TU5 line. In contrast, four out of 10 milk macrophage preparations lacked detectable spontaneous killing activity on this target. In vitro exposure to partially purified fibroblast interferon (IFN) or to lymphokine supernatants from PHA stimulated lymphocytes augmented the direct tumoricidal activity of blood monocytes and peritoneal exudate macrophages. Milk macrophages were completely unresponsive to IFN and lymphokines. therefore the capacity to mediate antibody-dependent and -independent cytotoxicity against tumour cells can be dissociated to some extent in human mononuclear phagocyte populations from diverse anatomical sites.

Animals↗
PubMed1980

Natural killer activity of lymphoid cells isolated from human ascitic ovarian tumors.

Lymphocytes and tumor cells were isolated from the carcinomatous ascites of 24 patients with epithelial ovarian tumors by stepwise application of density and velocity sedimentation on discontinuous Ficoll-Isopaque gradients and fetal bovine serum. Tumor-associated lymphocytes showed a lower percentage of cells with receptors for sheep erythrocytes (E) or for complement than did peripheral blood lymphocytes from the same patients. NK activity was measured, 51Cr-labelled K562 cells being used as targets in a 20-h assay. Tumor-associated lymphocytes showed significant NK activity. Cytotoxicity levels were lower than for peripheral blood effector cells from the same patients, and these in turn showed significantly lower cytotoxic capacity than peripheral blood lymphocytes from 64 control subjects. Similar results were obtained when lysis was measured after 4 h of incubation. Tumor-associated lymphocytes forming E rosettes were at least as effective as the unseparated population. When tumor-associated lymphocytes were mixed with normal effector cells, in three of six preparations with low NK activity tested, significant inhibition of normal lymphocyte NK activity was observed. Adherent macrophages from carcinomatous ascites, which contained lymphocytes that had suppressive activity, showed no inhibitory activity. Interferon (IF) boosted the NK activity against K562 of tumor-associated lymphocytes. Purified ovarian carcinoma cells were relatively resistant to lysis by normal lymphocytes. However, they inhibited lysis of K562 cells in cold target competition assays, though less efficiently than K 562 itself, and were consistently lysed when effector cells were stimulated with IF. It is therefore suggested that ovarian carcinoma cells express NK-relevant recognition structures, but are relatively resistant to cytolysis by unstimulated effector cells.

Ascitic Fluid↗
PubMed1980

Low-dose cyclophosphamide versus adriamycin plus cyclophosphamide in advanced ovarian cancer. A randomized clinical study.

After intensive staging 74 ovarian cancer patients were randomized to two arms balanced for stage and post-surgery residual tumor. The two regimens were CTX 100 mg/day continuously and ADM 50 mg/m2 IV every 4 weeks plus CTX 100 mg/day. The response rates were respectively 42% and 52%. Median survival times were 13 and 14 months. The incidence of side effects was significantly higher in the combination-treatment arm. No other statistical differences were found.

Adult↗
PubMed1980

Cytotoxicity on tumor cells of peripheral blood monocytes and tumor-associated macrophages in patients with ascites ovarian tumors.

Mononuclear phagocytes were isolated from the peripheral blood (PB) and ascites tumors of 35 patients with epithelial ovarian tumors. After 48 hours of incubation with the TU5 tumor, tumor-associated macrophages (TAM) and PB monocytes from cancer patients showed lower cytolytic activity than did control cells, but by 72 hours there was little difference between control and ovarian cancer effector cells. Primary ovarian carcinoma cultures were heterogeneous in their susceptibility to macrophage cytotoxicity. Tumor cells from 7 patients were significantly lysed by monocytes and macrophages, whereas four ovarian cancer cell preparations were resistant to cytotoxicity. A "feeding" effect of mononuclear phagocytes on non-lysable tumor cells was detected in terms of both lower [3H]thymidine-release values in the cytolysis assay and increased proliferation in cytostasis assays. Thus patients with ovarian carcinomatous ascites PB monocytes and TAM had impaired cytotoxicity against a tumor cell line, and primary ovarian carcinoma cultures were heterogeneous in their interaction with mononuclear phagocytes.

Adenocarcinoma↗