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Biomedical subjects

V Lorusso

Publications and source records attributed to V Lorusso.

At least 109 records · Page 6Linked to original sources

Sequential alternate administration of tamoxifen and medroxyprogesterone acetate in advanced breast cancer: clinical-biological randomized study.

From January 1985 to September 1988, 60 women with advanced breast cancer were randomized in two arms to receive: A) tamoxifen (TAM) (20 mg/die) until progression or B) TAM (20 mg/die for 14 days) then medroxyprogesterone acetate (MPA) (1500 mg/die p.o. for 14 days) followed by 7 days of wash-out before repeating the TAM/MPA treatment. All patients were post-menopausal, previously untreated with hormone therapy, and with tumor receptor status determined immediately before randomization; all had objectively evaluable lesions. In order to verify hormone receptor variations due to the antiestrogen, when possible a second biopsy was performed after the initial 14 day cycle of TAM. Thirty-one and 29 patients were included respectively in arms A and B. Objective regression (CR + PR) was observed in 58% of group A and 75% of group B, with CR in 11% and 23%, respectively. Differences were not statistically significant. Median time to progression was 12 months for group A and 9 for group B. Overall survival has not yet been reached in group A while it was 34 months for patients of group B. Metrorrhagia was observed in two cases of group A and in 6 of group B, and thrombophlebitis in 1 and 3 cases, respectively. The second biopsy confirmed a clear increase of PgR content in 8/11 cases (75%). Plasma level variations of TAM, N-desmethyl TAM and MPA were checked at various intervals on 3 patients of group B, and confirmed that our schedule is able to produce a drug wash-out period for tumor cells. In conclusion, our study demonstrated that while the manipulation of hormone receptors seems possible, results indicating better overall survival and time to progression were not obtained with alternate sequential TAM-MPA therapy.

Antineoplastic Combined Chemotherapy Protocols↗

High-performance liquid chromatographic assay of iomeprol in plasma and urine.

A high-performance liquid chromatographic method for assaying the radiographic contrast agent iomeprol in plasma and urine samples is described. Before reversed-phase chromatography, the biological fluids are treated with ion-exchange resins and iopamidol is added as internal standard. The compounds are monitored during elution by ultraviolet-visible spectrometry at 245 nm. The method shows good precision and accuracy and gives similar results to X-ray fluorescence analysis.

Chromatography, High Pressure Liquid↗

The role of tumour markers in ovarian cancer.

In the present review, the Authors have evaluated the current status of the utilization of the principle tumor markers for ovarian carcinoma in clinical gynecological practice. The major difficulty in individualizing a single marker is represented by the histological differentiation of the tumor itself. In fact, whereas for the malignant germ cell tumors, useful markers (AFP, B-HCG) are already available, for other histological forms, valid markers have been identified only because of the availability of the monoclonal antibody: CA 125. Even if this marker cannot be proposed for mass screening, it represents a useful instrument for the diagnosis and monitoring of ovarian carcinoma. The serum levels are well correlated with the clinical status of the patient and high concentrations of the marker are strongly indicative of disease progression at the second-look. Numerous other markers such as NB 70K, IAP, PLAP, CA 15-3 and TAG 72, are actually in the clinical evaluation phase, for the most part in association with CA 125.

Antigens, Neoplasm↗

Ovarian bilateral cystic teratomas: diagnosis and therapy in a young woman.

A case of ovarian bilateral cystic teratomas is described in young women. Difficult problems concerning diagnosis and therapy are deeply analyzed because of the rarity of this case. Bilateral and typical ultrasound aspects appear strongly indicative of an ovarian tumor. A conservative reproduction-preserving procedure was performed, due to the young age of the patients.

Adolescent↗

Intraocular lens complications.

The authors implanted intraocular lenses (IOL) in 780 eyes and considered complications of this surgery, dividing the complications into intraoperative and postoperative, the latter early and late. The most frequent intraoperative complications were: hyphema, vitreous injury, pupil deformation with an IOL in the anterior chamber (AC), and hyphema and corneal lesions with an IOL in the posterior chamber (PC). Among the early postoperative complications of an IOL in the AC the authors noticed striate keratopathy and uveal flare and postoperative transitory ocular hypertension and striate keratitis with an IOL in the PC. Moreover, in late postoperative complications in AC implantation they observed: cystoid macular edema, bullous keratitis, retinal detachment, late uveitis, opacification of posterior capsule, eccentric displacement of the IOL, and less frequently, cystoid macular edema in PC implantations. The authors prefer IOL implantation in the PC after extracapsular cataract extraction, since this surgery causes less problems in the cornea, vitreous, and retina.

Anterior Chamber↗

Cell kinetics and hormonal receptor status in inflammatory breast carcinoma. Comparison with locally advanced disease.

The biological and prognostic role of hormone receptor status and proliferative activity have been studied in two series of patients affected by inflammatory breast carcinoma (IBC, 28 patients) and locally advanced breast cancer (LABC, 50 patients). Estrogen receptor (ER) and progesterone receptor (PgR) were measured by dextran-coated charcoal (DCC) method whereas proliferative activity was measured by 3H-thymidine autoradiographic labeling index (LI). The percentages of ER+ and PgR+ cases resulted lower in IBC than in LABC (ER+, 44% versus 64%; PgR+, 30% versus 51%, respectively), pertaining to both premenopausal and postmenopausal women. Inflammatory breast carcinoma showed a higher median LI value than LABC (3.5% versus 1.6%; P = 0.006). Regarding clinical aspects, time to progression (TTP) in IBC patients was not affected by hormone receptor status (19 evaluable patients) or by LI (17 evaluable patients); PgR+ status and low LI resulted important for individualizing women with a longer median overall survival (OS). Inflammatory breast carcinoma has been verified to be a heterogeneous biological entity for which hormone receptors and cell kinetics could be useful in identifying patients with different prognoses and therefore candidates for a personalized therapy.

Adult↗

Comparison of CHOP-B vs CEOP-B in 'poor prognosis' non-Hodgkin's lymphomas. A randomized trial.

Sixty consecutive previously untreated patients with non-Hodgkin's lymphomas (intermediate or high grade and/or bulky disease and/or presence of constitutional symptoms), were randomized to receive either CHOP-B or CEOP-B (31 and 29 patients, respectively) to compare the therapeutic activity and toxicity. Complete response was observed in 65% of the patients treated with CHOP-B and 62% with CEOP-B; relapse of the disease occurred, respectively, in 5/20 (25%) and 6/18 (33%) of CR. Relapse-free survival and overall survival at 5 yr resulted in both groups (RFS 68% and 62% and overall survival 62% and 62%, respectively). In addition, increasing the dosage of epirubicin did not result in an increase in the haematologic toxicity or percent of CR. The haematologic toxicity was slightly lower in CEOP-B. The cardiologic monitoring (Eco 2D and EKG-Holter) at 400 mg mq-1 of EDX and ADM did not demonstrate variations in cardiac function in the CEOP-B group, while in the ADM patients the ejection fraction was statistically lower as regards basal values. In conclusion, in our randomized study, substitution of ADM with EDX in non-Hodgkin's lymphomas in the CHOP-B regimen, did not decrease the therapeutic activity of the combined chemotherapy, while less toxicity (haematologic and cardiac) was observed. For these reasons, in our opinion, epirubicin can substitute adriamycin in second and third generation regimens for non-Hodgkin's lymphomas in which the major drawback for a wider diffusion is the severe toxicity observed.

Adult↗

Intravenous administration of cyclophosphamide, methotrexate and 5-fluorouracil in metastatic breast cancer. A pilot study.

Sixty-two women with advanced breast cancer were admitted to a pilot study in which a modified CMF regimen was administered. Cyclophosphamide was administered i.v. at a dosage of 600 mg/m2 on the same day as fluorouracil (600 mg/m2/i.v.) and methotrexate (40 mg/m2/i.v.). The therapy was recycled on the 21st day and in the presence of myelosuppression, the administration of the drugs was delayed for 1-2 weeks recovery of the hematologic values. CR + PR were obtained in 42% of patients and no change in 32% (U.I.C.C. criteria). Metastases to soft tissues showed CR + PR in 55% of the cases, bone in 33% and viscera in 35%. The menopausal status, the disease-free interval and the number of involved sites did not influence statistically the percentage of responses; however, the response rate was influenced statistically by previous treatment. The median duration of response was 7.5 months; the median overall survival of the 60 evaluable patients was 18 months. Due to myelosuppression, CMF i.v. administration was delayed 90/620 times (14%). Toxicity was acceptable and had a lower incidence than that reported in the literature in different series of CMF administered p.o. Nausea and vomiting, in particular, were limited to 24-48 h after administration of the drugs, and alopecia was seldom observed.

Administration, Oral↗

CA 125 in the monitoring of response to chemotherapy of ovarian carcinoma.

CA 125 serum levels were assessed in 23 patients undergoing chemotherapy for advanced epithelial ovarian carcinoma (EOC). Rising, falling and unchanged levels correlated with disease in 21 out of 23 (95%) cases. Ten out of 11 patients who showed objective response to chemotherapy had a decrease in antigen levels. Two out of 3 patients with stable disease had unchanged values. Progression was always associated with rising levels. CA 125 is a reliable marker for monitoring response to chemotherapy in advanced epithelial ovarian carcinoma.

Adult↗

Relevance of cell kinetics to hormonal response of receptor-positive advanced breast cancer.

The relationship between cell kinetics and hormonal status and the relevance of the cell kinetic variable on success of hormone-therapy in estrogen receptor positive (ER+) breast tumors were analyzed in patients with advanced disease. Cell kinetics were evaluated as in vitro 3H-thymidine labeling index (LI), and estrogen receptor (ER) and progesterone receptor (PgR) with the dextran-coated charcoal technique. The analyses performed on primary tumor or soft tissue metastases from 52 patients showed a general association between the presence of hormone receptors and low proliferative activity, or the absence of receptors and high proliferative activity (ER and L.I.: p greater than 0.05; PgR and L.I.: p = 0.05). However, hormonal status and cell kinetic status were unrelated in about 40% of the cases. Clinical response to additive hormonotherapy was analyzed in relation to pretreatment LI in 29 patients with ER+ tumors. Time to reach maximum response was significantly longer in slow than in fast proliferating tumors, but complete remission was reached in 88% of slow proliferating tumors compared to only 46% of fast proliferating tumors. These preliminary results show that ER+ fast proliferating tumors largely escape hormonal control, and if confirmed on larger series, could identify cell kinetics as an important tool to select patients who will benefit from hormonal treatment.

Adult↗

B-19036, a potential new hepatobiliary contrast agent for MR proton imaging.

B-19036 is an octadentate chelate of the paramagnetic ion Gd3+ under investigation as a proton relaxation enhancer (PRE) in magnetic resonance (MR) proton imaging. Its relaxivity was determined at 0.5 T by pulse spectrometry in various biologic fluids and in liver tissue homogenate. The ligand selectivity versus gadolinium was assessed in comparison with that versus other ions of biologic interest. Acute toxicity was determined after intravenous (IV) and intracerebral administration to mice. Pharmacokinetic studies conducted in rats indicated that unlike Gd-DTPA, where excretion is exclusively renal, biliary route plays a significant role in the excretion of B-19036, suggesting its possible use for hepatobiliary imaging.

Acetates↗

[A formulation of iopamidol for the radiologic examination of the gastrointestinal tract. Preclinical studies].

Animal studies were carried out using an oral solution of a low osmolality non ionic contrast medium iopamidol, developed for gastrointestinal examinations. The new formulation was evaluated for image quality in studies of the upper and lower gastrointestinal tract. Margins of safety were defined by subjecting the compound to a number of toxicological and pharmacological experiments. The experiments were designed to reveal qualitative and quantitative differences between the formulation of iopamidol and Gastrografin, a conventional ionic contrast medium. The results indicate that the formulation of iopamidol is safer than a conventional hypertonic water soluble contrast medium and diagnostically superior in the gastrointestinal tract examinations.

Animals↗

Chemotherapy and surgery in the treatment of ovarian cancer bulky disease.

Thirty-six patients with stage III-IV ovarian cancer, bulky disease, were treated with adriamycin and cyclophosphamide administered in two different dosages. Three or four cycles of chemotherapy were administered before the first surgery to facilitate the surgical debulking. After surgery, 6 additional cycles of chemotherapy were administered, and a second look was performed. Clinical CR + PR was observed in 19/30 (63%) evaluable patients after the first part of chemotherapy, but pathologic CR + PR was confirmed in only 13 (43%) patients. After the second part of chemotherapy and the second surgery, 5/30 (17%) patients had pathologic CR and 3/30 (10%) showed residual disease. The two regimens demonstrated similar activity (67% vs 56% clinical CR + PR) but a very different toxicity. In fact, 50% of patients treated with higher doses showed severe leukopenia and 25% severe thrombocytopenia, and 2/13 died of sepsis. The significant activity of adriamycin plus cyclophosphamide in ovarian cancer was confirmed, and increasing the dosage of the two drugs did not increase their activity but only their toxicity.

Adult↗

Cisplatin plus etoposide as second-line treatment in advanced ovarian carcinoma.

We have treated 25 consecutive patients with advanced ovarian carcinoma with cisplatin (100 mg/m2 iv on Day 1) and etoposide (100 mg/m2 orally on Days 1-3) every 3 weeks. All patients had failed previous treatment with doxorubicin and cyclophosphamide and had bulky abdominal disease. Complete response was achieved in one of 25 patients (4%), partial response was achieved in nine of 25 patients (36%), and stable disease was obtained in six additional patients (24%). Median time to disease progression was 6.8 months. Toxicity was acceptable. Cisplatin and etoposide is an effective second-line treatment of ovarian carcinoma.

Adult↗

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma.

Cis-diamminedichloroplatinum (CDDP) was administered i.v., at the dosage of 20 mg/m2 for 5 consecutive days and recycled every 3 weeks, to 11 patients with bidimensionally measurable metastatic lesions from bladder cancer previously untreated with antineoplastic drugs. Eight patients (6 men and 2 women) were evaluated for clinical response and 9 for toxicity. No complete regression was observed, and partial regression was obtained only in 3 patients (37.5%). Severe leukopenia and thrombocytopenia occurred only occasionally; moderate nausea and vomiting were observed in 5 cases. Nephrotoxicity was noted in 4 of the 9 patients evaluable for toxicity, and 2 of them, with ureteral obstruction, died of renal failure.

Adult↗

Determination of intraperitoneal mitoxantrone in the serum of cancer patients using a high performance liquid chromatograph coupled to an Advanced Automated Sample Processor (AASP).

A study has been carried out on 10 patients with ovarian cancer treated by intraperitoneal mitoxantrone. The serum concentration was determined by high performance liquid chromatography with spectrophotometric detection. The extracted analyte on the cartridge was injected and eluted on-line into the analytical column by the mobile phase. This improved the signal and sample processing rate, without significant loss in analytical performance. Excellent linearity (r greater than 0.9994) was observed for the calibration curve over the range 1-2000 ng/mL, along with a precision within-day and between-day estimated as 1.5% and 5.6%, respectively. Sensitivity was an order of magnitude higher than that of the comparison method. From a clinical point of view, these preliminary results have shown that intraperitoneal administration is more beneficial than intravenous therapy. Low serum levels (1-30 ng/mL) with a maximum at the first or second hour are revealed.

Aged↗

Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as 'sponges' of Gd3+ ions.

MR-labeling of cells may be carried out by adding a Gd-based contrast agent to the incubation media. The amount of gadolinium internalized in HTC and C6 cells upon incubation with Gd-DTPA-BMA is circa one order of magnitude higher than those found with Gd-DTPA, Gd-DOTA and Gd-HPDO3A, respectively. The comparison of relaxometric and mass spectrometry determinations allows us to establish that only a minor fraction of intact Gd-DTPA-BMA is internalized into the cells. Moreover the binding/uptake behavior shown by Gd-DTPA-BMA resembles that found when GdCl(3) is added to the incubation medium. We suggest that the lower stability of Gd-DTPA-BMA is responsible for a shift in the dissociation equilibrium that results in the net transfer of Gd(3+) ions on the cell membrane followed by a slower internalization process. The transmetallation process is mediated by components of the incubation media, among which a dominant role is represented by phosphate anions. The uptake of Gd(3+) ions is clearly reflected in the drastic decrease of cell viability observed for cells labeled with Gd-DTPA-BMA.

Animals↗

Immunoglobulin heavy chain gene rearrangement in B-cell non-Hodgkin's lymphomas detected by the polymerase chain reaction.

AIMS AND BACKGROUND: Immunoglobulin heavy chain gene rearrangement serves as a marker of clonality and cell lineage in B-cell lymphoproliferative disorders. In this study we used the polymerase chain reaction (PCR) to detect clonal rearrangements of the immunoglobulin heavy chain gene in a group of patients with B-cell lymphomas. METHODS: DNA was extracted from frozen tissue of 40 B-cell non-Hodgkin's lymphomas and subjected to PCR amplification using primers that recognize conserved sequences of the variable and joining regions of the immunoglobulin heavy chain gene. RESULTS: Monoclonal rearrangements were detected in 23 of 40 malignant B-cell lymphomas. No clonal rearrangements were detected in the 10 control cases. CONCLUSIONS: We conclude that this PCR-based technique may provide a simplified and rapid approach for the detection of clonal immunoglobulin heavy chain gene rearrangements in B-cell lymphomas without recourse to Southern blotting, which can be reserved for cases in which PCR is negative.

Base Sequence↗