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Biomedical subjects

M A Gerosa

Publications and source records attributed to M A Gerosa.

33 records · Page 2Linked to original sources
PubMed1983

Stem cell studies of human malignant brain tumors. Part 1: Development of the stem cell assay and its potential.

A stem cell assay for human malignant gliomas has been developed. Cells obtained from tumor biopsies grew into colonies composed of malignant glial cells, as documented by histochemical, immunohistochemical, and immunobiological techniques. Studies suggest that the disaggregated cells are representative of the cells within the solid tumor. Clonogenic cells were obtained from 48 tumors and analyzed for their in vitro sensitivity to graded doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The in vitro anti-tumor activity of BCNU at clinically achievable doses was compared to clinical response to the agent based on changes in computerized tomographic scan, radionuclide brain scan, and neurological examinations. Twenty-two patients received nitrosoureas before or after tumor specimen analysis, and were eligible for in vitro-in situ correlations. Clinical tumor sensitivity to nitrosoureas was predicted by culture results in 42% of all evaluable patients, and clinical resistance was predicted in 100%. The capability of the assay can be appreciated best for the 13 patients not treated with BCNU prior to culture; the in vitro prediction of clinical sensitivity and resistance was 71% and 100%, respectively. Preliminary findings show that clinical tumor resistance to BCNU may result from "intrinsic" cell resistance in some patients and from inadequate delivery of drug to tumor cells in other cases. The potential utility of this method to study the reason(s) for tumor cell resistance to drugs, to screen new chemotherapeutic agents, to individualize patient treatment, and to investigate tumor biology is discussed.

Biological Assay↗
PubMed1983

Improved treatment of a brain-tumor model. Part 1: Advantages of single- over multiple-dose BCNU schedules.

Clonogenic cell and animal survival studies were used to determine the most effective BCNU therapy schedule in the 9L rat brain-tumor model. Survival of tumor cells following a single LD10 dose of BCNU (13.3 mg/kg intraperitoneally) was compared to cell survival after one to four daily 0.5 X LD10 doses. The posttreatment kinetics of surviving clonogenic cells were investigated at various times after BCNU was given in single doses of 0.25 to 1 X LD10 and in two daily doses of 0.5 X LD10. The cell kill was greater, time to reinitiation of cell growth was later, posttreatment rate of clonogenic cell proliferation was slower, and the interval to total repopulation of the clonogenic cell pool was longer with a single LD10 dose as compared to the multiple-dose schedules. Animal survival studies confirmed that a single LD10 dose of BCNU was at least as effective as a cumulative level of up to 1 1/2 times that amount when treatment was administered in smaller doses, regardless of the fractionation schedule. Clinical experience with patients harboring malignant brain tumors has shown that a single BCNU dose of 185 to 200 mg/sq m is tolerated well. Results of these animal experiments suggest that this therapy should have anti-tumor activity at least equivalent to the more commonly employed schedule of 80 mg/sq m/day given for 3 days. Although direct comparison of treatment efficacy using the two schedules is not possible, no adverse clinical effects have been observed with the recently adopted single-dose schedule. Furthermore, the duration of patient hospitalization for chemotherapy has decreased.

Animals↗
PubMed1983

Improved treatment of a brain-tumor model. Part 2: Sequential therapy with BCNU and 5-fluorouracil.

A combination chemotherapy regimen for brain tumors was developed, based on investigations of the survival of animals harboring the intracerebral 9L rat brain-tumor model and on analyses of their clonogenic tumor cells. Fischer 344 rats harboring 9L brain tumors were treated with 2-day courses of 5-fluorouracil (5-FU), in order to expose all cycling tumor cells to the drug during DNA synthesis and achieve maximum anti-tumor activity for this cell-cycle-specific anti-metabolite. Although a 74% cell kill was obtained for a total dose of 45 mg/kg or greater, animal life span was not increased over that of untreated tumor-bearing controls. However, when 5-FU (48 to 96 mg/kg total dose over 2 days) was administered after a single LD10 dose of BCNU (13.3 mg/kg), additive cell kill was suggested. In three large series, long-term animal survivors and occasional tumor cures were observed with this drug combination, a result never observed following BCNU alone. Schedule dependency was not apparent. A previously published protocol for treating recurrent malignant gliomas with sequential courses of BCNU and 5-FU was partially planned based upon these initial observations. Anti-tumor activity with the combination of drugs was superior to therapy with BCNU alone. Both animal and human studies confirm that, contrary to presently accepted oncological tenets, a chemotherapeutic agent that kills significant numbers of tumor cells but is clinically ineffective when given alone might, nevertheless, be useful in combination therapy regimens.

Animals↗
PubMed1982

Impaired immunocompetence in patients with malignant gliomas: the possible role of Tg-lymphocyte subpopulations.

T-lymphocyte subpopulations (Tg or "suppressor cells" and Tm or "helper cells") in the peripheral blood of 16 patients with malignant intracranial gliomas were analyzed. The number of Tm-lymphocytes was very close to normal in both pre- and postoperative samples, whereas Tg-lymphocytes were significantly increased preoperatively (18.55 +/- 1.11 vs. 12.72 +/- 1.19 p less than 0.001) and were still slightly higher than normal after operation and radiation treatment. These preliminary findings suggest a possible role of T-suppressor lymphocytes in the impairment of cell-mediated immunocompetence that has been observed repeatedly in patients with malignant gliomas.

Adolescent↗
PubMed1981

VM-26 monochemotherapy trial in the treatment of recurrent supratentorial gliomas: preliminary report.

Twenty-five adults with recurrent supratentorial malignant gliomas were treated with VM-26 in a monochemotherapy schedule, the antiblastic region covering a period of 24 weeks. Five cases were excluded from the final evaluation, 4 because of protocol violations and 1 due to intolerance to the drug. In the group of 20 patients who met the criteria for evaluation, 7 (35%) showed a partial or complete response, with clinical or radiological tumor aggression, and the conditions of 7 (35%) were unchanged at the end of the chemotherapy courses. The progression-free intervals turned out to be 10.4 months and 8.5 months, respectively. Six patients (30%) complained of tumor progression despite the treatment. Most of the patients are still alive, and the actuarial survival rate is encouraging. Toxicity was mainly hematologic, but usually moderate and easily reversible.

Anemia↗
PubMed1981

Cerebrospinal fluid levels of cyclic nucleotides and monoaminergic metabolites in subarachnoid haemorrhage: preliminary report.

c-AMP, c-GMP, HVA and 5 HIAA cerebrospinal fluid levels were investigated in 18 patients with subarachnoid haemorrhage (SAH). The main findings in the acute stage after SAH were represented by a marked increase of c-AMP and 5 HIAA values, whereas HVA levels were only slightly higher. In the chronic phase c-GMP levels turned out to be significantly increased, and were clearly related to intracranial hypertension. 5 HIAA and particularly HVA levels were decreased, probably due to the functional and anatomical lesion of the periventricular adrenergic structures, following the raised intracranial pressure.

Acute Disease↗
PubMed1981

Multidisciplinary treatment of medulloblastoma: a 5-year experience with the SIOP trial.

A 5-year experience of the multidisciplinary treatment of pediatric medulloblastoma with the SIOP (International Society of Pediatric Oncology) trial is presented. 33 eligible patients finally reduced to a total of 30 evaluative cases were treated with major surgical resection, extensive irradiation, and combined chemotherapy (vincristine + CCNU). The overall survival rate without recurrence was encouraging, and the actuarial survival rate is satisfactory. At follow-up controls, most of the patients showed a good performance status and a promising neurological stage. However, the problem concerning quality of life remains unsolved: morbidity and sequelae following high-dose radiotherapy and concomitant antiblastic treatment were noticeable.

Adolescent↗
PubMed1981

Cerebral arteriovenous malformations in children (56 cases).

A survey of 56 patients aged less than or equal to 16 years, admitted (1954-1979) for cerebral arteriovenous malformations, is presented. The clinical manifestation was mostly related to hemorrhage, less frequently to epilepsy or to a cerebral 'steal' syndrome. The most frequent site was the parietal lobe, with supply from the middle cerebral artery. Deep malformations were not uncommon and most lesions were of medium or large size. 38 patients were operated upon, and 18 were given treatment other than surgical (including radiotherapy). 23 malformations were completely excised, in 4 patients only a partial excision could be carried out, and in 10 patients surgery consisted of occlusion (clipping or coagulation) of feeding vessels. In 1 patient, surgery had to be limited to removal of an intracerebral hematoma. The immediate and long-term results of treatment are much better in the surgical than in the nonsurgical group.

Adolescent↗
PubMed1980

Cerebrospinal fluid levels of cyclic nucleotides in non-neoplastic hydrocephalus: preliminary report.

Cerebrospinal fluid levels of cyclic nucleotides in children with hypertensive communicating hydrocephalus secondary to leptomeningitis were investigated. 3':5'-cAMP and 3':5'-cGMP values were uniformly increased in pre-operative findings, suggesting a "passive" behaviour of the blood brain barrier after the inflammatory lesion. After ventriculo-peritoneal shunt, the mean ratio between the two nucleotides gradually became negative, with a marked increase of cGMP levels, probably related to selective barrier damage. In patients with shunt obstruction, the altered cAMP/cGMP ratio showed a gradual regression towards normal, due to a decrease in the cGMP level. The important role of endocranial pressure changes in the "second messenger" turnover is stressed.

Blood-Brain Barrier↗
PubMed1980

Immunobiology of primary CNS tumors in infancy and childhood. B- and T-cell dependent immunity and cytotoxicity and cell kinetic evaluation.

The authors report their experience on the immunological monitoring of children with posterior fossa medulloblastomas. The most important findings concerning humoral and cell-mediated immunity in this kind of patient are discussed. Among the main immunobiological pictures, the authors stress the remarkable failure of the T-cell dependent immune response, generally correlated to the degree of malignancy of the tumor, and the characteristic appearance of cells with natural cytotoxic activity, whose precise outlining is, at present, in progress. The B-cell dependent pool, mostly investigated through immunofluorescence studies, turned out to be very close to normal.

B-Lymphocytes↗
PubMed1980

Cyclic nucleotides in medulloblastomas: correlative study of tumoral and cerebrospinal fluid levels.

The tumoral and cerebrospinal fluid (CSF) levels of cyclic nucleotides and of the main adrenergic metabolites (homovanillic acid and 5-hydroxyindoleacaetic acid) were investigated in a group of children with posterior fossa medulloblastomas. A longitudinal evaluation of CSF change of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and adrenergic metabolites before and after surgical removal of the tumor mass is presented. Some preliminary patterns concerning correlative levels in the neoplastic tissue are discussed. The relevant increase of cGMP in medulloblastoma specimens and in CSF samples operation and the rapid decrease in the CSF after surgical removal of the tumor seem to suggest a possible role of cyclic nucleotides in the neoplastic growth of these tumors. (Neurosurgery, 7: 359-362, 1980).

Blood-Brain Barrier↗
PubMed1980

CSF levels of cyclic nucleotides and adrenergic metabolites in malignant gliomas.

Recent advances indicate that cyclic nucleotides and perhaps certain adrenergic metabolites might be directly involved in contact-inhibition mechanisms and tumoral cell growth. CSF levels of 3'-5' cAMP, 3'-5' cGMP, HVA, and 5-HIAA were investigated in patients with supratentorial malignant gliomas, brain stem gliomas and posterior fossa medulloblastoma. cAMP levels were slightly decreased only in medulloblastomas, whereas no significant difference was detectable in patients with supratentorial gliomas. cGMP values turned out to be significantly higher, with a very peculiar increase in the most anaplastic neoplasms. Postoperative follow-up showed a gradual decrease of cGMP values, with progressive restoring of a normal cAMP/cGMP ratio. The possible correlation of these findings with CSF levels of HVA and 5-HIAA is discussed.

Adult↗
PubMed1980

Clinical and experimental immunobiology of medulloblastomas.

A wide pre- and postoperative immunological monitoring of B- and T-cell markers in children with medulloblastomas is presented. Preoperative investigations showed a noticeable failure of T-cell-dependent immunity, currently identified by "active" E-rosette forming cells (Ea-RFC) and blastogenesis tests, with a significant increase of spontaneous cell-mediated cytotoxicity (SCMC). In postoperative long-term controls, a slight recovery of Ea-RFC and blastogenesis tests was observed. The main findings concerning cytotoxicity kinetics are discussed.

Adolescent↗
PubMedDate not supplied

Spontaneous ("erosive") cerebrospinal rhinorrhea, with pneumococcal meningitis from anterior optic glioma. Case report.

A 6-year-old girl, operated upon for an optic nerve astrocytoma (resection limited to the intraorbital portion of the nerve), developed 3 years later symptoms and signs of chiasmatic invasion. Nine years after surgery (1980), she suffered from pneumococcal meningitis, due to cerebrospinal rhinorrhea that had been present in the last few years. A repeated neuroradiological investigation showed the site of the fistula and cerebral ventricles of normal size. The case is argued for bulb-to-chiasm resection of an optic nerve glioma: a spontaneous cerebrospinal rhinorrhea with its potential dangers of meningitis seems to be one more complication of a limited resection of these tumors. It is felt that this is an unusual instance of spontaneous rhinorrhea from direct tumoral erosion. The diagnostic value of metrizamide cisternography for the assessment of presence and site of the fistulous leak is confirmed.

Adolescent↗