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Biomedical subjects

R Knerich

Publications and source records attributed to R Knerich.

At least 19 recordsLinked to original sources
PubMed1996

CNS-85 trial: a cooperative pediatric CNS tumor study--results of treatment of medulloblastoma patients.

Between 1985 and 1989, 38 children with newly diagnosed medulloblastoma entered our therapeutic protocol. After surgery and postoperative staging assessments, patients were assigned to risk groups. Eleven with "standard-risk" (SR) tumors were treated with radiation therapy alone, while 27 with "high-risk" (HR) tumors received radiation therapy plus adjuvant chemotherapy with vincristine, methotrexate, VM-26, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). After a minimum follow-up of 5 years (range 5-9 years) 21/38 children had developed a recurrence or progression of their disease and 19/38 patients had died. Five-year event-free survival rates and 5-year total survival rates for all 38 patients were 47.4% and 50% respectively. The event-free survival rates at 5 years for SR and HR patients separately were 27.3% and 55.6%, respectively. The corresponding 5-year total survival rates were 27.3% and 59.3%. The differences were not statistically significant. Univariate analysis showed age at diagnosis to be the most important prognostic factor. Infants aged 5 years or less had a significantly shorter event-free survival time than older patients (P = 0.00897). Similar effects were found when total survival time was considered. There were significant differences in outcome in patients receiving different doses of radiation, suggesting a dose-response relationship. A Cox stepwise multivariate analysis showed age at diagnosis as the only independent prognostic factor. Variables relating to treatment entered the model, suggesting that chemotherapy could play an important role in determining outcome.

Adolescent↗
PubMed1991

Concentrations of VP16 and VM26 in human brain tumors.

VP16 and VM26 were determined by high pressure liquid chromatography in intracerebral tumors, adjacent normal brain tissue, plasma and CSF samples from 24 patients given the two drugs before surgical resection of the tumor. The drugs were administered at doses of 100-150 mg/m2 as a 1-hour i.v. infusion, between 1.5 and 12 hours before surgery. Concentrations of VP16 ranged between 1.05 and 3.28 micrograms/g in tumors in the series of patients who received the drug 1.5-3 hours before surgery and between less than 0.05 and 1.12 micrograms/g in four patients who received the drug 9-13 hours before surgery. Tumor concentrations of VM26 also varied, ranging from less than 0.05 to 1.68 micrograms/g between 1.5 and 12 hours before surgery. VP16 and VM26 in the apparently normal brain tissue surrounding the tumor were low or undetectable except in one patient who had received radiotherapy, in whom we found 3.1 micrograms/g.

Adult↗
PubMed1991

"Ex vivo" release of eicosanoid from human brain tissue: its relevance in the development of brain edema.

The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The "ex vivo" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Chemotherapy for malignant gliomas of the brain: a review of ten-years experience.

In recent years, there has been a great improvement in the knowledge of the biological aspects of malignant gliomas of the brain. Conversely, there has been an increase of interest in the multimodal treatment of these tumours. In this review, we have analyzed the results of the several reports which have appeared in the literature that deal with the chemotherapeutic treatment of malignant gliomas. Furthermore, some areas of biological investigation that could have an impact on pharmacological therapy are discussed.

Antineoplastic Agents↗
PubMed1988

Cell kinetics aspects of human malignant neuroepithelial tumors: a follow-up study.

The prognostic value of proliferative activity and DNA distribution (ploidy), determined by flow cytometry (FCM), was evaluated in 38 cases of human malignant neuroepithelial tumors. No statistically significant correlation was found between flow cytometric data and clinical outcome. In particular, there was no significant difference between mean survival in cases with percentage of cells in S-phase lower and higher than 5%, respectively. In 21 cases with unimodal DNA distribution, the mean survival was 11.7 months; in 17 cases with bimodal DNA distribution, the mean survival was 12.5 months. The difference was not statistically significant. In our experience, proliferative activity and ploidy do not correlate well with the clinical course and survival of patients with malignant neuroepithelial tumors. However, application of FCM may provide, aside from histopathologic examination, additional biologic information that may be valuable in understanding the variation observed in the course of individual patients.

Adult↗
PubMed1987

Recessive cancer genes in meningiomas? An analysis of 31 cases.

Cytogenetic studies on 31 human meningiomas revealed clonal abnormalities in 14 of them. Monosomy 22 was present in three cases as the only abnormality, and in five it was associated with monosomy 18, monosomy 14, loss of X, loss of Y, and trisomy 20, respectively. We found a number of rearrangements involving chromosome #22: an i psu dic(22)(pter----q11::q11----pter) in two cases and a t(18;22)(q12;q11) in another case. Two cases showed a complex translocation involving #7 and #14: t(2;7;14)(q23;q36;q22) and t(1;7;14)(q25;q32;q22), respectively. Other clonal chromosome abnormalities were del(1p) (present in two cases); der(9)t(9;?)(q34;?); der(7)t(7;?)(q31;?); der(22)t(22;?)(q11;?); and a 9p+ chromosome. The relevance for the pathogenesis of human meningiomas of these chromosome anomalies is also discussed with reference to the previous literature. The possible involvement of recessive cancer genes present on the long arm of chromosome #22 is also discussed.

Adult↗
PubMed1987

Nitrosourea derivatives-induced pulmonary toxicity in patients treated for malignant brain tumors. Early subclinical detection and its prevention.

Nitrosourea derivatives, such as BCNU and CCNU, are considered useful chemotherapeutic agents in malignant brain tumors combined therapy. Pulmonary toxicity is one of the major side effects demonstrated both in experimental animal models and in human autoptic findings. Pulmonary fibrosis is the end point of progressive functional disorder of respiratory mechanism and alveolo-capillary gas exchanges. Authors present the results of a randomized, double-blind trial of 40 patients previously treated with surgery and radiotherapy and who subsequently underwent BCNU therapy for primary intracranial glioma. Patients underwent functional respiratory examinations at each chemotherapy course interval. Twenty patients received ambroxol (120 mg/day) for 40 days after chemotherapy course. Control patients received placebo with the same schedule and showed a significant reduction of pulmonary functional parameters (DLCO, MMEF, MEF 25%), whereas in the treated group there is no significant variation of these functional parameters. The mechanism of ambroxol is commonly related to the surfactant synthesis enhancement and to the action on bronchiolar pathways.

Adult↗
PubMed1987

Ploidy and proliferative activity of human brain tumors. A flow cytofluorometric study.

Ploidy and proliferative characteristics were estimated by flow cytometry of the nuclear DNA content of 92 human brain tumors. Samples were frozen at -20 degrees C immediately after surgery and single cell suspensions were obtained with a mechanical dissociation technique. Propidium iodide was employed for nuclear DNA staining. Human normal brain tissue was used as internal diploid reference standard. 86% of benign tumors had unimodal DNA distribution with a DNA index (DNA I = modal channel of the G0/1 peak of the studied population/modal channel of the G0/1 peak of the normal brain) usually within the diploid or near-diploid range. 14.0% had aneuploidy, with an additional cell peak having a median DNA I of 1.60. Among malignant tumors, these figures were 61.2 and 38.8% (p less than 0.001). The percentage of S phase cells was higher in malignant (median = 3.6) than in benign tumors (median = 2.0, p less than 0.01), without correlation to histological tumor subtype. Flow cytometry appears to be a useful method for evaluating differences in DNA distribution in tumors of the central nervous system.

Adolescent↗
PubMed1986

Ambroxol and pulmonary toxicity induced by antineoplastic drugs.

The authors describe the potential effects of ambroxol on the pulmonary disorders induced by antineoplastic agents (in particular, bleomycin and the nitrosureas). An experimental stage focussed attention on the early modifications occurring in the alveolar surfactant and in the afflux of inflammatory and immune-effector cells following bleomycin-induced lung fibrosis in the rat (by intratracheal instillation). The ambroxol-protected rats showed a slower drop of alveolar lecithins in the first few hours after bleomycin administration and a lower afflux of neutrophils, macrophages and lymphocytes. In the clinical stage, respiratory function was studied in two groups of cancer patients treated with nitrosureas or bleomycin. Preliminary findings indicate a rapid worsening of some functional parameters--maximal expiratory flow at 25% vital capacity, diffusing capacity for carbon monoxide and diffusing capacity/ventilation--in controls, while no such changes occurred in the ambroxol-protected subjects. The possible pathogenetic implications of these results and perspective for future investigations are discussed.

Ambroxol↗
PubMed1986

Proliferative characteristics and ploidy of human brain tumors by DNA flow cytometry.

We studied nuclear DNA distribution by flow cytometry in 59 human brain tumors. Samples were frozen at -20 degrees C immediately after surgery and unicellular suspensions were obtained with a mechanical dissociation technique. Nuclear DNA was stained with propidium iodide. Normal human brain tissue was used as a diploid reference standard. In 86.3% of benign tumors an unimodal DNA distribution with a DNA index usually within the diploid range was found. Among malignant tumors, 64% had un unimodal DNA distribution with diploid or near-diploid modal DNA content. The remaining 36% showed an additional cell peak with a DNA index ranging from 1.15 to 1.92. The percentage of S-phase cells was higher in malignant (median = 3.8) than in benign tumors (median = 1.9) (p less than .001), without correlation to histological tumor subtype.

Aneuploidy↗
PubMed1984

[Chemotherapy of malignant brain tumors in childhood].

The best conventional care for medulloblastoma and malignant ependymoma in children consists of surgery and radiotherapy. The preliminary observations of some authors suggested that chemotherapy could be useful in treating these tumors. The two major experiences in this field are those from SIOP and CCSG -RTOG trials which used chemotherapy as adjuvant to surgery and radiotherapy. In such studies chemotherapy appears to be effective mostly in high-risk patients. A study performed by Italian Child's Neurooncology Group ( ICNG ) confirms the preceding results.

Adolescent↗
PubMed1984

[Chemotherapy, immunotherapy and supportive therapy in cerebral metastases].

When a malignant tumor spreads to the brain, its concurrent growth outside of the Central Nervous System (CNS) and the devastating effects of cerebral metastases offset often all therapeutic attempts. The disappointing results commonly achieved in the management of intracranial metastases are only partly explained by the low efficacy of available therapeutic modalities. Support therapy plays the major role in the management of patients harboring cerebral metastases. Corticosteroids and osmotic agents can rapidly improve neurological symptoms, allowing a rapid, even if frequently brief, amelioration of the quality of life. Immunotherapy cannot be considered as an effective therapeutic tool for metastatic brain tumors. For many years chemotherapy has been thought inadequate treatment for both controlling the growth of metastases and improving neurological impairment . However the new concepts of multimodality therapy of primary CNS tumors seem to be applicable even to intracranial metastases. In combination with corticosteroids and radiation therapy, nitrosourea compounds (BCNU and CCNU) proved to be effective in more than 1/3 of patients in prolonging survival. New possibilities of improving available results are expected from new antiproliferative drugs (cisplatin) and from new modalities of administering conventional cytotoxic agents (intra-arterial route).

BCG Vaccine↗
PubMed1984

[Chemotherapy and immunotherapy of intracranial malignant gliomas].

Although in recent years a great attempt has been made in brain tumor chemotherapy, this therapeutic approach appears to be conditioned by a large number of problems such as cell kinetics, tumor growth modalities, and drug delivery. Therefore only a small number of drugs (BCNU, CCNU, streptozotocin, and procarbazine) clearly demonstrate effectiveness against these tumors. Immunotherapy raises the same and other problems. In fact, if immune reaction is quite possible inside the brain, unfortunately current immunostimulant methods are unable to produce significant improvements.

BCG Vaccine↗
PubMed1984

[Steroid receptors in brain tumors].

Recently the presence of steroid hormone receptors (SHR) have been reported in a series of nervous system human tumors, mainly in meningiomas. The possibility of characterizing brain tumors deserves attention because of the poor knowledge of endocrine-related behaviour of such tumors. The reliability of biochemical characterization of various receptor types should allow for better understanding of biological profile of primary and metastatic brain tumor, together with new avenues for combined modality treatment. In the future the highest priority might be assigned to the definition of the cut-off value of positivity for single receptors and to the receptor-endocrine modulation complex relationship for individual patients. A clear definition of the role of SHR in human brain tumors might improve our therapeutic potentials.

Brain Neoplasms↗
PubMed1984

Radio-chemo-immunotherapy (CCNU plus levamisole) for treatment of metastatic brain tumors. A pilot study.

Thirty-one patients with metastatic brain tumors were treated with Radiotherapy (RT) and CCNU or with RT, CCNU and Levamisole (LMS) in a randomized clinical trial. Twenty-seven were evaluable. All patients were submitted to whole brain radiation (50 +/- 5 Gy) and CCNU (130 mg/m2 p.o. every 8 weeks). 15 also received Levamisole (2.5 mg/kg p.o. daily for 3 weeks in the first month, for 2 weeks in the second, and then once a week monthly until progression). Primary tumor was predominantly lung cancer (22/27) and brain lesions were generally multiple (24/27). The overall response rate was 35% in the RT plus CCNU treated group and 38% in the RT plus CCNU plus LMS treated group. The median survival time was similar and not statistically different in both groups (7 versus 6 months). No important side effects were observed either in the RT + CCNU or in the RT + CCNU + LMS treated groups. The absence of combined depression of T-cell levels and responsiveness of lymphocytes to mitogens suggests that thymus dependent immunity could be improved by LMS administration. However, such improvement had no impact on duration of survival in patients with metastatic brain tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Clinical toxicity of combined modality treatment with nitrosourea derivatives for central nervous system tumors.

Two nitrosourea compounds--1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)--have been used in the treatment of primary and metastatic brain tumors after operation and/or radiotherapy. Hematological and nonhematological toxicity were recorded in 272 patients treated between May 1973 and June 1978. BCNU was given to 135 patients (80 mg/m2 i.v. daily for 3 days) and CCNU was given to 137 patients (130 mg/m2 orally, single dose) every 8 weeks until progression of the primary disease process or for a total of 12 cycles. Radiation therapy (5500 +/- 500 rads in 6 to 7 weeks) was carried out after the first course of chemotherapy. BCNU and CCNU induced the same hematological and clinical toxicity. The bone marrow toxicity seemed to be dose-related, delayed, and cumulative. One case of acute nonlymphoblastic leukemia arising 2 months after the end of CCNU therapy is reported.

Bone Marrow Diseases↗