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Biomedical subjects

F Landoni

Publications and source records attributed to F Landoni.

At least 73 records · Page 4Linked to original sources

Procoagulant and fibrinolytic activity of human ovarian carcinoma cells in culture.

We have investigated here the coordinate expression of both procoagulant (PCA) and fibrinolytic (FA) activity of cells from 16 human ovarian carcinoma cases. To avoid interference of contaminating host cells, we used cells isolated in primary culture from ascitic fluid or from solid tumor. The FA was determined in cellular extracts by an amidolytic assay in the presence of fibrin monomers. FA, which was plasminogen dependent in almost all of the cases, showed a wide range of activity (from less than 0.001 to 2.30 UK units/mg protein). The molecular analysis of plasminogen activator (by SDS-PAGE and fibrin autography) showed a single molecular form of 52,000 daltons, inhibited by an antibody against human urokinase. PCA, studied with a one stage clotting assay in disrupted cells, was of tissue thromboplastin type in all instance and varied from 12.0 to 1300 thromboplastin units/10(4) cells. No simple correlation was found between FA and PCA in the cellular samples studied; moreover, for neither parameter was it possible to find any changes with the staging of the disease.

Adult↗

Effect of tamoxifen on steroid hormone receptors and creatine kinase activity in human endometrial carcinoma.

Estrogen receptor (ER), progesterone receptor (PR) and creatine kinase (CK) were measured in cancerous tissue from 29 post-menopausal patients with endometrial carcinoma under basal conditions and after a short course of tamoxifen treatment. ER and PR were detected in nearly all tumors. CK was detected in all of the tumors examined. After tamoxifen, PR and CK increased simultaneously in 26% of cases, while they were either enhanced, decreased or unmodified in the remainder. No correlation could be found between increase of PR and tumor differentiation. CK, however, was enhanced only in the more differentiated cancers. These results indicate that only a percentage of endometrial cancers are responsive to tamoxifen. It is hypothesized that patients bearing these tumors are those likely to benefit from endocrine therapy.

Cell Transformation, Neoplastic↗

Mitozolomide activity on human cancer cells in vitro.

The growth inhibitory effects, the reduction of [3H]-TdR incorporation and the perturbation of the cell cycle induced by the new agent mitozolomide on the M14 human melanoma cell line and on the SW626 human ovarian cancer cell line were compared to those produced by BCNU. Flow cytometry showed an interesting difference: at the high concentration mitozolomide induced an accumulation of cells in S middle and S late-G2-M phase of the cell cycle whereas BCNU caused only a block in S late-G2-M. Further studies were aimed at investigating the susceptibility of freshly isolated human ovarian cancer cells to pharmacologically reasonable mitozolomide concentrations. Only in one out of 16 primary cultures of human ovarian cancers was mitozolomide able to induce cell cycle perturbation, suggesting that ovarian carcinoma cells may not be sensitive to this drug.

Aged↗

Evaluation of the interaction of mononuclear phagocytes with ovarian carcinoma cells in a colony assay.

The effect of human peripheral blood monocytes on the SW626 ovarian carcinoma line was investigated in a colony assay in agar, Percoll-enriched monocytes inhibited colony formation by SW626 carcinoma cells at effector-to-target cell (E:T) ratios as low as 0.3:1. In contrast the same effectors had little cytolytic effect in a 48 h thymidine-release assay at E:T ratios as high as 40:1. Monocyte-depleted nonadherent cells had little inhibitory capacity on SW626 colony formation, whereas unseparated mononuclear cells were intermediate between Percoll-enriched monocytes and lymphoid cells. Sorting of cells positive for the monoclonal antibody marker MO2 confirmed the monocytic nature of cells which inhibited colony formation. Ovarian carcinoma cells freshly isolated from 9 patients were heterogenous in their susceptibility to colony inhibition by mononuclear phagocytes. Cells from 4 patients were not inhibited by effector cells and in one subject promotion of colony formation by mononuclear phagocytes was observed. With 4 cell preparations inhibition of colony formation was found as with the SW626 line. Colony assays may provide a useful methodological approach, particularly when effector cells mediate low levels of killing, of doubtful biological significance, in conventional isotope release assays, or when growth promotion is to be evaluated.

Cell Line↗

Cisplatin, vinblastine, and bleomycin combination chemotherapy in metastatic granulosa cell tumor of the ovary.

Eleven previously untreated women with recurrent and/or metastatic granulosa cell tumor of the ovary were treated with cisplatin, vinblastine, and bleomycin in combination. All the six pathological complete responders but one are alive and free of disease at a median follow-up time of 14 months from the start of treatment. Of three partial responders, two died of drug-related toxicity while one, with only microscopic disease at second-look laparotomy, is alive and without evidence of disease at 34 months. Hematologic and nonhematologic toxicity were severe. These promising results require further examination of the activity and the best schedule of treatment with this combination.

Adult↗

DNA index of ovarian carcinomas from 56 patients: in vivo in vitro studies.

Out of 130 ovarian cancer patients the DNA index of cells from ovarian carcinoma was studied in 56 cases in which cytospin preparations showed the presence of atypical cells. In 24 patients the population had a diploid DNA index (1.0) and in the others the DNA index ranged from 1.2 to 2.0 (tetraploid). No hypodiploid or hypertetraploid populations were detected. Repeated samples from the same patients did not show any significant differences and primary culture did not alter the DNA index. In contrast, cell cycle phase distribution differed greatly from sample to sample, as also the ratio between DNA diploid and DNA aneuploid populations. Primary culture was successful in 57% of the tumours, with a higher percentage of success in DNA aneuploid tumours. After primary culture the ratio between DNA aneuploid cells and DNA diploid cells increased. In relation to the histological gradings of malignancy, DNA aneuploid cells clustered in the highest grade of malignancy. The mean S-phase for tumours with a DNA index of 1.0 was 3.5 and 14.1% for those with DNA index greater than 1. Ovarian carcinomas show a large difference in DNA index between patients even after primary culture.

DNA, Neoplasm↗

Clinical correlates of in vitro drug sensitivities of ovarian cancer cells.

Of 89 samples of cancer cells from ovarian cancer patients primary cultures representative of the cancer cell population could be established in 17. The clinical response to polychemotherapy was studied in relation to the inhibition of thymidine uptake by the cultured cells. Cultures of each patient's tumour were exposed to concentrations of the drugs the patients had been given for long enough to reproduce the area under the curve (AUC) of the plasma levels resulting from in vivo dosage. Full agreement was observed between the degree of thymidine uptake inhibition induced by at least one of the drugs administered to the cultured cells and the degree of clinical response. This approach may prove useful in pharmacological studies as a means of obtaining ovarian cancer cell populations representative of human tumours, even though the number of tumours that can be successfully evaluated in vitro is still too small to serve as a sound basis for prediction.

Adult↗

Clinical behavior of 203 stage II endometrial cancer cases: the impact of primary surgical approach and of adjuvant radiation therapy.

The aim of this study was to verify the impact of primary surgical approach and adjuvant radiation therapy (RT) on survival, recurrence rate, and pattern of relapse in stage II endometrial cancer patients. Two hundred three subjects were retrospectively reviewed; 135 (66%) underwent simple hysterectomy (SH) and 68 (34%) radical hysterectomy (RH). Sixty-six of 111 (59%) of stage IIA and 67 of 92 (73%) of stage IIB patients underwent adjuvant radiation therapy. Actuarial survival rates for stage IIA and IIB were 86% and 74% at 5 years and 82% and 68% at 10 years, respectively. Survival rates by surgical procedure were 79% in the SH group and 94% in the RH group at 5 years and 74% and 94% at 10 years, respectively (P < 0.05). The overall recurrence rate was 13.8% (28/203); by adjuvant treatment it was 18.6% (13/70) in the observation group and 11.3% (15/133) in the RT group. Most of the relapses were locoregional in the observation group and distant in the RT group. Survival rates by RT were not statistically different. Subjects treated with RH improved their survival compared with the SH group; the difference was significant, but randomized studies should confirm this trend. Although adjuvant RT seemed to reduce the recurrence rate, there was no significant difference in survival, and so the role of RT still needs further verification.

Adenocarcinoma↗

Factors influencing survival in endometrial cancer relapsing patients: a Cooperation Task Force (CTF) study.

The purpose of this study was to identify patterns of relapse and to determine the outcome of salvage treatment and the factors influencing survival of endometrial cancer relapsing patients. One thousand six hundred and six endometrial cancer (stages I to IV) patients treated at five Italian institutions were retrospectively reviewed. Of these, 209 (13%) subjects had recurred; the site of relapse was vagina in 35 cases (16.7%), pelvis in 67 (32.1%), and distant locations in 107 (51.2%). Most of the patients relapsed within 24 months: 45% (94) recurred within 1 year, 20.6% (43) between 1 and 2 years. Adjuvant radiotherapy (RT) seemed to reduce the percentage of pelvic recurrence in high risk early stages (IB-IIA) subjects and a higher proportion of patients failed at a distant site when postoperative external-beam pelvic RT was given. However survival curves were not statistically different in the two groups for stage IB endometrial cancer patients. Five and 10-year survival rates of patients with recurrent disease was 26% and 22%, respectively. Relapse of endometrial cancer is often early and at distant sites. Survival rate was related to site of relapse, disease-free interval, and postoperative treatment as independent prognostic variables. The site of relapse is the most important predictor of survival of patients with recurrent disease.

Adult↗

Brain metastases from cervical carcinoma.

Central nervous system (CNS) involvement by cervical carcinoma is uncommon. Out of 1,184 patients registered for invasive cervical carcinoma at our institution between 1982 and 1994, 14 (1.18%) developed brain metastases. Median age at the time of CNS metastasis diagnosis was 52 years. Median interval between diagnosis of cervical cancer and documentation of brain involvement was 18 months. Clinical manifestation included motor weakness, headache, seizures, dizziness and visual disturbances. All lesions (8 multiple, 6 single) were contrast enhanced on computerized tomography scans and were located in the cerebrum (n = 10), in the cerebellum (n = 2), or in both (n = 2). The CNS was the only site of detectable disease in 7 patients with recurrent disease. Eleven patients received only steroids, and 3 patients received radiotherapy. All 14 patients died, and median survival from diagnosis of brain metastases for the entire series was 4 months (range, 1-21). CNS metastases from cervical cancer are rare, and the prognosis for such patients appears poor.

Adenocarcinoma↗

Concurrent carboplatin/5FU and radiotherapy compared to radiotherapy alone in locally advanced cervical carcinoma: a case-control study.

AIMS AND BACKGROUND: Despite the introduction of innovative techniques in radiotherapy (RT) delivery, no significant improvement in survival has been achieved in the last decades. Concurrent chemoradiation therapy (CRT) is one of the several avenues being explored to improve the results. METHODS AND STUDY DESIGN: Twenty-eight women with locally advanced squamous cell carcinoma of the uterine cervix were treated with CRT comprising a combination of external and intracavitary RT, along with 3 cycles of 5-fluorouracil (5-FU) and carboplatin. Toxicity, pelvic control rate and disease-free survival achieved in this group of patients were compared in a case-control study with those of a group of 28 patients with similar clinico-pathologic characteristics treated with radical RT alone at our institution. RESULTS: CRT was well tolerated, with 97% of the patients completing the protocol as planned. Acute toxicity, primarily hematologic, was significantly (P = 0.05) higher in the cases than in the controls (25% vs 3%). One treatment-related death occurred in a stage III patient in the CRT group. The median follow-up was 55 months (range, 20-156) in the RT group and 20 months (range, 14-46) in the CRT group. Pelvic control rate, disease-free survival and overall survival were not significantly different in the two groups. Estimated 5-year survival rate was 70% and 66% respectively for the RT and CRT group. CONCLUSIONS: Concomitant carboplatin/5-FU and radiotherapy is a safe and tolerable means of treatment for locally advanced cervical cancer. In our study, however, concurrent CRT did not result in a significant improvement in pelvic control rate or survival compared to standard conventional radiotherapy.

Adult↗

Neoadjuvant chemotherapy to radiation and concurrent chemoradiation for locally advanced squamous cell carcinoma of the cervix: a review of the recent literature.

Radiotherapy is the standard treatment for locally advanced cervical cancer; nevertheless it fails to control disease progression within the irradiation fields in more than 40% of cases, particularly in patients with bulky tumor. Distant metastases are not infrequent in more advanced cases. Chemotherapy has been integrated with radiotherapy to improve local control and treat distant subclinical metastases. Schedules of combined treatment more frequently represented by neoadjuvant chemotherapy followed by radiation (NACT) and by concomitant chemotherapy and radiation (CT-RT). A review of the recent literature is presented. The role of NACT is controversial: high response rates are reported but doubtful advantages in terms of survival or local control have been shown. In randomized trials, hydroxyurea concomitant to radiation improves local control and survival, particularly in stage IIIB and IVA. Several randomized trials of concurrent chemoradiation with 5FU, cisplatin and mitomycin C are underway, but few have been published: no significative differences are reported in term of local control or survival. Acute toxicity is higher than in radiation alone, but usually manageable. For the analysis of late morbidity a longer follow-up is required. Large randomized trials of adequate radiotherapy versus concomitant chemoradiation are necessary to refine our understanding of the benefits of this integrated treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Brachytherapy for isolated vaginal recurrences from endometrial carcinoma.

AIMS AND BACKGROUND: Isolated vaginal recurrences of endometrial carcinoma are rare, and prognostic factors that predict treatment outcome are still not well defined. The aim of the present study was to evaluate the results of brachytherapy in isolated vaginal recurrences from endometrial carcinoma. METHODS: Thirty-five patients with isolated vaginal recurrences were treated with brachytherapy with intravaginal ovoids or cylinders that were calculated to deliver 6000 to 7000 cGy at the surface. Patients were assessed for size and location of recurrence at presentation, response and complications from therapy. RESULTS: Treatment was well tolerated by most patients. Grade 2 toxicity occurred in 4 patients (3 cases of partial vaginal stenosis and one proctitis). Complete response to radiation was observed in all patients, and an overall 9 failures were observed (4 local, 4 distant and 1 local plus distant). Twenty patients (57%) were alive without evidence of disease at 3 to 11 years following treatment. Site of vaginal recurrence (upper third versus others) and long (more than 12 months versus less than 12 months) interval from hysterectomy were the only factors significantly related to local failures. CONCLUSIONS: Isolated vaginal recurrences following hysterectomy for endometrial carcinoma can be treated with brachytherapy with a low rate of severe toxicity.

Aged↗

A role for tumor markers in therapeutic decisions after chemotherapy induction of objective remission in stage III epithelial ovarian neoplasms.

The management of advanced stage ovarian carcinomas is presently based on initial surgical debulking, multiple drug chemotherapy including cisplatinum, second-look laparotomy. Such an aggressive approach has improved objective response rates and expected survival time, but no dramatic change has been demonstrated as for definitive cure percentages. Many Authors have attempted to turn an optimal objective response to chemotherapy (no residual or minimal residual disease at second-look) into a definitive cure with irradiation. Some reports show satisfactory results, but a high incidence of bowel obstructive complications has been demonstrated, probably due to multiple surgical manipulations before radiotherapy. A reliable diagnostic tool, that could help to avoid the second-look laparotomy (whose inherent role in improving survival is not assessed) should be therefore useful. The possible role of serum tumor markers determinations, for this purpose, is here discussed on the ground of a series of 20 patients affected by stage III ovarian carcinoma. Following this experience, a valuable role seems attributable to CA 125 in monitoring tumor response. Patients achieving values under 35 U/ml before second-look laparotomy showed tumor residuals in the range O-microscopic- less than 1 cm., that is, neoplastic localizations reliable for consolidation radiation therapy.

Adenocarcinoma↗