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Biomedical subjects

C Dominici

Publications and source records attributed to C Dominici.

At least 55 records · Page 3Linked to original sources

Effects of a single course of deferoxamine in neuroblastoma patients.

A phase II trial of a single 5-day course of deferoxamine in 9 patients with neuroblastomas was completed. Within 2 days of completion of treatment responses were observed in 7 of 9 patients and there was no drug toxicity. These responses were a decrease in bone marrow infiltration and, in one patient, a measurable reduction in her tumor mass. We conclude that deferoxamine given as an 8-h i.v. infusion daily for 5 days at 150 mg/kg/day has antitumor activity.

Adolescent↗

High-dose carboplatin in combination with etoposide (JET regimen) for childhood brain tumors.

Fourteen patients aged 1 to 15 years with medulloblastoma (six patients), low-grade astrocytoma (four patients), and high-grade astrocytoma (four patients) were treated with carboplatin and etoposide (JET regimen). Six patients had been treated previously, two of them with cisplatin at conventional doses. Carboplatin was administered at 500 mg/m2/day over 5 h on days 1 and 2, in association with pulsed etoposide at 100 mg/m2/day on days 1, 2, and 3. Courses were repeated at 3-week intervals. The disease-specific response rates were as follows: five of six with three complete responses and two partial responses for medulloblastoma; zero of four for low-grade astrocytoma; and two of four with two partial responses for high-grade astrocytoma. Myelosuppression was the main side effect: anemia (hemoglobin less than 8.0 g/dl), thrombocytopenia (less than 25,000/microliter) and leukopenia (less than 1,000 white blood cells/microliters) were noted in 19 of 54, 10 of 54, and 7 of 54 courses, respectively. Gastrointestinal toxicity was very mild, and nephro- and neurotoxicity were not observed. No audiometric abnormalities were demonstrated in seven of seven patients who had not previously received cisplatin, and preexisting audiometric abnormalities were not worsened by the administration of carboplatin in one cisplatin-pretreated patient. The combination of carboplatin and etoposide administered in this study appears to be effective and well tolerated in children with brain tumors. Further studies on a larger number of patients are needed to ascertain its real activity in childhood brain tumors.

Adolescent↗

A pilot study of high-dose carboplatin and pulsed etoposide in the treatment of childhood solid tumors.

Carboplatin was administered at 1,000 mg/m2/course in combination with etoposide at 300 mg/m2/course to 23 patients aged 5 months to 16 years. Five patients were affected by neuroblastoma, four by CNS tumors, three by Ewing's sarcoma, two by rhabdomyosarcoma, two by malignant teratoma, two by Wilms' tumor, two by head and neck carcinoma, one by hepatoblastoma, one by synovial sarcoma, and one by Langerhans-cell histiocytosis. Eleven patients were pretreated, seven of them with high-dose cisplatin. The overall response rate was 7/11 (64%) for pretreated and 10/12 (83%) for previously untreated patients. Myelosuppression was the main side effect, with anemia and thrombocytopenia more pronounced than leukopenia. Gastrointestinal toxicity and ototoxicity were very mild; nephrotoxicity and neurotoxicity other than hearing loss were not observed. In children with malignant tumors, the therapeutic activity of carboplatin at high doses, even in combination chemotherapy, deserves further studies.

Adolescent↗

[Endodermal sinus tumor. Histological changes induced by chemotherapy].

The case of a child affected at birth sacrococcygeal teratoma is reported. Twenty-eight months following surgical resection, the tumor relapsed locally and liver metastases occurred. A biopsy of the sacrococcygeal mass was performed and histologic examination proved it to be an endodermal sinus (yolk sac) tumor. Chemotherapy consisting of etoposide and high-dose carboplatin was started. When a second operation was performed the mass had disappeared and the macroscopically involved areas of liver were removed. Histologic examination demonstrated that the complete necrosis of the tumor was partially replaced by a fibrous scar tissue. The child underwent adjuvant chemotherapy and now is in complete remission fourteen months after the last operation.

Antineoplastic Combined Chemotherapy Protocols↗

Establishment and characterization of a human neuroblastoma cell line.

A continuous human cell line RN-GA was established from a stage-III primary neuroblastoma prior to therapy. Light and electron microscopic analysis of the biopsy showed morphological features typical of neuroectodermal origin. Relative cellular DNA content and N-myc oncogene copy number were also analyzed in the biopsy tissue: the tumor cells presented a near-diploid genome with N-myc amplification. The derived tumor cell line expressed distinctive ultrastructural, cytogenetic and immunological markers of neuroblastoma. Moreover, cells from the culture could be serially transplanted into splenectomized-irradiated nude mice, where they formed a progressively growing solid tumor. Surprisingly, the cells in culture did not show any N-myc amplification, while they retained a near-diploid DNA content. We propose that several techniques (electron microscopy, oncogene analysis, flow cytometry, cytogenetics, tissue culture, cell antigen immunodetection) should be used to establish a firm diagnosis and a correct clinical grading of this tumor. The establishment of this continuous cell line should be valuable as an experimental in vitro system for further studies of neuroblastoma biology and morphology.

Adrenal Gland Neoplasms↗

[Aneurysm of the innominate artery: pathology simulating pulmonary neoplasm].

A chance case of aneurysm of the brachiocephalic trunk suggested a review of the literature on this rare pathology. Stress is laid on the possible asymptomaticity of the lesion and on its frequent chance observation in chest X-rays; the diagnostic procedure, at times particularly complex, may not lead to decisive results but the possibility of aneurysm of the brachiocephalic trunk must be borne in mind in any case so as to avoid gross diagnostic and therapeutic errors.

Aged↗

A pharmacokinetic study of high-dose continuous infusion cisplatin in children with solid tumors.

The pharmacokinetics of cisplatin were investigated in 14 patients, aged 10 months through 13 years who were affected by solid malignant tumors. High-dose cisplatin (40 mg/m2/d) was administered with repeated courses for five days as a continuous intravenous (IV) infusion. Total platinum (Pt) levels in plasma and urine and free (protein-unbound) Pt levels in plasma ultrafiltrate were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Areas under the concentration v time curve (AUCs) for mean total and free Pt levels were calculated for the 120-hour period of infusion and for the 384 and 120 hours following its completion, respectively. Half-lives of total and free Pt in plasma were calculated for the 216 hours following completion of infusion in five patients at their first course. The fraction of the administered Pt dose excreted in urine as Pt was determined for the five-day period of infusion and seven-day period after its completion. A total of 36 courses were studied. Maximum average Pt levels were reached after 120 hours of infusion: at the first course, 3.22 and 0.17 micrograms/mL for total and free Pt, respectively. Platinum levels declined according to a biexponential model, with initial half-lives of 18.3 and 16.9 minutes, and terminal half-lives of 81.9 and 59.0 hours as determined for total and free Pt, respectively. In the second and third courses studied there was a progressive increase in mean Pt plasma levels. Consequently, the free drug exposure as measured by AUC increased in all patients with repeated courses: 47.7% for the second and 124.4% for the third course, when compared with the first. At the same time, the mean fraction of the dose excreted in the urine for the 12-day period considered, was 44.1% for the first course, 36.2% for the second, and 28.4% for the third. The progressive enhancement of tissue exposure to the free cytotoxic drug, resulting from a reduced renal clearance of Pt with sequential courses of cisplatin, produced mainly increased toxicity while therapeutic effect progressively diminished.

Adolescent↗

Clinical, analytical and pharmacokinetic aspects in cancer chemotherapy with platinum coordination compounds.

A survey of investigations performed by our group over the last few years whose goal was to obtain analytical, clinical and pharmacokinetic data concerning cancer chemotherapy with Pt-based drugs is reported. From this standpoint the use of inductively coupled-plasma atomic emission spectrometry for determining Pt levels in biological samples is discussed, particularly as regards: 1) the amelioration of sample introduction procedures into the torch in the case of micro-sampling and 2) the investigation of plasma drug distribution by means of liquid chromatography techniques. Clinical studies evaluated therapeutic response and toxicity during regional and systemic treatments with Cisplatin and Carboplatin against solid tumors in adults as well as in children. Several pharmacokinetic parameters such as plasma half-lives for free and protein-bound drug, tissues exposure as determined by AUC and urinary excretion are examined.

Adolescent↗

Occupational exposure to antiproliferative drugs in health care workers.

A survey is presented of the information available on the occupational hazard caused by exposure to anticancer drugs. Emphasis is laid on the need for stricter and safer measures to protect the sanitary personnel, who should also be constantly and thoroughly informed on the risk run when manipulating antiproliferative agents. Possible strategies for effectively preventing occupational diseases in this field are finally outlined.

Abnormalities, Drug-Induced↗

Bilateral rhabdomyomatous tumor relapsed as typical triphasic Wilms' tumor.

The authors report on a child affected with bilateral renal tumor, which was treated with cancer chemotherapy before and after surgery. Twenty-eight months after the discontinuance of therapy, a neoplasm was disclosed in the left kidney and then removed. Histologically, the bilateral tumor excised by the first surgery could be classified as biphasic Wilms' tumor, rhabdomyomatous variant, whereas the neoplasm removed by the second surgery was the typical triphasic Wilms' tumor. The authors suggest that preoperative chemotherapy might have played a role in the histologic changes of the initial tumor. Nonetheless, it is also tempting to postulate that the two histologic variants of Wilms' tumor could have occurred in the patient in spite of any treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Determination of Pt in biological samples by inductively coupled plasma atomic emission spectrometry (ICP-AES) with electrothermal vaporization (ETV).

An electrothermal sample vaporization device was combined with an inductively coupled plasma spectrometer for the determination of Pt in biological samples (serum, urine, tissues). A commercial graphite furnace for atomic absorption was connected to an ICP torch using an electrically heated quartz tube. The argon gas stream was slightly modified. Sample aliquots up to 100 microL were dried at 120 degrees C, ashed at 1400 degrees C and subsequently heated to 2700 degrees C. The aerosol obtained was transported into a 2.2 kW argon ICP by means of a carrier gas flowing at 1.4 L/min. The detection limit was found to be 0.25-0.5 micrograms/L, depending upon the matrix. These values are one order of magnitude better than those obtained using conventional nebulizers. The precision (RSD) at 50 micrograms/L ranged from 0.04 to 0.07 and the accuracy (evaluated as recovery) was 103.2% to 105.3%. Because the matrix effects could not be neglected, different calibration curves were prepared for each kind of medium. The analytical capabilities of the method described were found to be suitable for the determination of Pt used in routine monitoring during chemotherapy with Cisplatin and other Pt-based compounds.

Hot Temperature↗

Correlation between tyrosine hydroxylase immunoreactive cells in tumors and urinary catecholamine output in neuroblastoma patients.

The results of an immunocytochemical evaluation of tyrosine hydroxylase (TH) immunoreactivity in 30 neuroblastic tumors of infancy are reported. Although no correlations could be found between the immunoreactive pattern and the site of origin or the staging of the tumor, a positive relationship between the urinary catecholamine output and the density of TH-immunoreactive cells could be established. TH was mostly localized on the cytoplasm of the differentiating neuroblasts, whereas immature elements were rarely positive. Moreover, 2 stage IVS cases did not contain any TH immunoreactivity. The possible significance of this finding in the investigation of this form of neuroblastoma, which has a peculiar biological behavior, is considered.

Catecholamines↗

Chemotherapeutic agent cisplatin monitoring in biological fluids by means of inductively-coupled plasma emission spectrometry (ICP-AES).

The antitumoral agent cis-diamminedichloroplatinum (II) was administered at doses of 40 mg m-2 body surface area daily for 5 days via continuous i.v. infusion in association with etoposide (VP-16-213). The Pt concentration in serum up to 30 days from the beginning of the therapy was monitored by inductively-coupled plasma emission spectrometry. Results lead to two main conclusions: the analytical technique employed is suitable for measurements of Pt in biological fluids with the necessary precision (0.95-2.5%), accuracy (recovery 98.5-101.7%) and detection power (0.002-0.004 mg/l); there were effective Pt plasma concentrations for a greater length of time (with peak value 2.0 mg/l towards the end of treatment) than those achieved by other therapies so far adopted. On the other hand, toxic side effects, in particular gastrointestinal toxicity, myelosuppression and nephrotoxicity, were found to be not worse than those generally caused by the administration of the chemotherapeutic compound at lower doses. Both aspects were deeded to be essential prerequisites for better exploiting the drug's effectiveness.

Body Fluids↗