RESUMO
The O-alkyl cleavage enzyme is important for the metabolism of cytotoxic alkyl-lysophospholipids. We have developed a simple new method for the determination of the enzyme activity which is based on the formation of water-soluble phosphate during the enzyme reaction. This is the first assay which avoids the use of radiolabeled substrates.
Assuntos
Hidrolases/metabolismo , Fosfolipase D/metabolismo , Fosfolipases/metabolismo , Fosfolipídeos/metabolismo , Pteridinas/metabolismo , Fosfolipases Tipo C/metabolismo , Animais , Lisofosfolipídeos , Microssomos Hepáticos/enzimologia , Ratos , Ratos EndogâmicosRESUMO
In a phase-II trial, 18 patients with intractable pelvic and perineal pain caused by local recurrent and/or metastatic colorectal carcinoma resistant to combinations of analgesics, systemic cytostatic chemotherapy and/or radiation were treated with intra-arterial perfusion therapy using 15-30 mg 5-FU/kg body wt./day for 1-5 days. Of 18 patients, ten achieved complete pain relief for 3-32 weeks (mean, 15.7 weeks); after the perfusion therapy eight used less than 50% of the amount of analgesics required before treatment; one patient had only a minor response; two patients were treated unsuccessfully. Side effects were mild and controllable. One patient died subsequent to arterial embolism in the leg where the catheter was placed; pelvic perfusion therefore appears risky in patients with severe arteriosclerosis.
Assuntos
Neoplasias do Colo/secundário , Fluoruracila/uso terapêutico , Infusões Intra-Arteriais , Dor Intratável/tratamento farmacológico , Neoplasias Retais/secundário , Adulto , Neoplasias do Colo/tratamento farmacológico , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/tratamento farmacológicoAssuntos
Cromossomos , RNA , Timo , Animais , Compostos de Boro , Bovinos , Cromatografia por Troca Iônica , DNA , Eletroforese Descontínua , Hibridização de Ácido Nucleico , Oxirredução , Peptídeo Hidrolases , Ligação Proteica , RNA/análise , RNA/isolamento & purificação , RNA de Transferência/isolamento & purificação , Ribonucleases , Espectrofotometria , Trítio , Raios UltravioletaAssuntos
Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Linfoma/tratamento farmacológico , Podofilotoxina/análogos & derivados , Adulto , Cisplatino/efeitos adversos , Quimioterapia Combinada , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Distribuição Aleatória , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VindesinaAssuntos
Neoplasias Colorretais/tratamento farmacológico , Garantia da Qualidade dos Cuidados de Saúde/economia , Quimioterapia Adjuvante/economia , Neoplasias Colorretais/economia , Neoplasias Colorretais/mortalidade , Terapia Combinada , Controle de Custos/tendências , Alemanha , Humanos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Adjuvant chemotherapy in women with breast cancer is currently regarded as standard procedure. An efficacy of 10-20% can only be viewed as modest, even if a statistically significant prolonging of disease-free interval and overall survival has been established. The value of this mode of therapy is questionable because 80-90% of patients are subjected to chemotherapy with no effect, i.e. they would either have remained well regardless, or they are primarily resistant. In both cases, they are prone to suffering significant side effects. The cost-benefit ratio also needs to be taken into consideration. It is therefore recommended that the therapeutic effect is depicted in absolute percentages and not in relative percentages and absolute numbers. Only rendering the results as absolute percentages allows a true comparison between the small number of patients who benefit and the vast majority who do not. Even if this mode of therapy is regularly implemented worldwide by doctors, requested by patients and understandably backed by industry, the central question remains: 'How great do the benefits of a particular therapy have to be, in order to justify its use? Who should set the limits?' For the time being it therefore does not appear to be a mistake not to subject the patients in question to chemotherapy, unless they are part of a study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante/economia , Ensaios Clínicos como Assunto , Terapia Combinada , Análise Custo-Benefício , Feminino , Humanos , Estadiamento de Neoplasias , Qualidade de Vida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Among 12 patients with hairy cell leukaemia two died without splenectomy and two more 11 months and 7 1/2 years after the operation. In all patients removal of hypersplenism led to improvement of haematological criteria over several months up to many years. This was particularly true for platelets and granulocytes and thus for the proneness to infection and haemorrhagic diathesis. In two patients normalisation of all haematological parameters including histologically scarcely detectable hairy cells was observed. Differential diagnosis from prolymphocyte leukaemia is difficult. Nuclear morphology permits recognition of different degrees of maturation of hairy cells. In cases where tartrate resistant acid phosphatase (TRAP) cannot be demonstrated cytologically, demonstration of isoenzyme 5 is sometimes possible using gel electrophoresis. Demonstration of TRAP remains valuable for the diagnosis of hairy cell leukaemia, however only in connection with other criteria indicating this form of leukaemia.
Assuntos
Leucemia de Células Pilosas/diagnóstico , Fosfatase Ácida/análise , Adulto , Idoso , Feminino , Humanos , Hiperesplenismo/complicações , Hiperesplenismo/cirurgia , Isoenzimas/análise , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/enzimologia , Leucemia de Células Pilosas/terapia , Masculino , Pessoa de Meia-Idade , EsplenectomiaRESUMO
This review article summarizes the results of cytostatic treatment for squamous carcinoma of the head and neck region between 1977 and 1980. The cytostatic therapy is not established yet. Dosage and combination of the three most effective drugs: Methotrexate, Bleomycin and Cis-Platinum seems to be of minor importance for the effectivity than selection of patients for prognostic factors. Primary chemotherapy in not pretreated patients with Karnofsky-Index above 60% is most successful.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Humanos , PrognósticoRESUMO
The cytochemical and gelelectrophoretic demonstration of acid phosphatases with substrates alpha-naphthyl phosphate and naphthol AS-BI phosphate and with couplers fast garnet GBC and hexazotized pararosanilin is described. Cytochemically best results are achieved wit naphthol AS-BI phosphate and pararosanilin, electrophoretically however with alpha-naphthyl phosphate and pararosanilin. This discrepancy ist explained by a different substrate affinity and membrane penetration of substrates.
Assuntos
Fosfatase Ácida/isolamento & purificação , Leucócitos/enzimologia , Eletroforese/métodos , Histocitoquímica , Humanos , Isoenzimas/isolamento & purificaçãoRESUMO
Forty-four patients, surgically and/or radiologically treated after primary cytostatic treatment, were compared by matched-pair analysis with a historical control group of patients who had been conventionally treated by surgery and/or radiotherapy only. Both groups were largely identical with respect of tumour localisation and classification, regional metastases, and conventional treatment. The disease-free survival and overall survival times did not differ significantly between both groups. It appears that tumour remission following primary cytostatic therapy does not influence survival times. Primary cytostatic treatment offers advantages over conventional therapy only if it is combined with surgical and radiological procedures in selected patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Bleomicina/administração & dosagem , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Laríngeas/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/tratamento farmacológico , Prognóstico , Vindesina/administração & dosagemRESUMO
The uptake of 14C-labeled aminoglutethimide into the brain was investigated in the rat after intracarotid injection according to the method of Oldendorf, as well as in cisternal cerebrospinal fluid obtained by suboccipital puncture after i.v. injection of the drug. The brain uptake index of aminoglutethimide after intracarotid injection was 30.7 + 2.4%. Cerebrospinal fluid/blood quotients after i.v. drug injection were 0.53 at 10 min and 0.26 at 60 min. The results of both methods clearly show that aminoglutethimide easily penetrates the blood brain barrier.
Assuntos
Aminoglutetimida/metabolismo , Barreira Hematoencefálica , Animais , Encéfalo/metabolismo , Permeabilidade , Ratos , Ratos Endogâmicos , Distribuição TecidualRESUMO
The activities of acid phosphatases (AP) were measured in leukocytes from patients with chronic myelocytic leukemia (CML), macrophages, granulocytes, in the fractionated mononuclear cells of patients with CML and with hairy-cell-leukemia (HCL) and in the cells from patients with acute leukemia (AL). The lowest activities were found in lymphocytes of normal subjects and of patients with chronic lymphatic leukemia (CLL) and in thrombocytes. Isoenzyme (IsE) 1 was characteristic for thymocytes, IsE 2 for granulocytes, IsE 3 for pathologic blast-cells, lymphocytes and thrombocytes, IsE 4 for macrophages, IsE 5 with components a and b for the mononuclear fraction of patients with HCL. In addition IsE 5 was detected in lymphocytes, macrophages and CLL-cells. In 4 patients with HCL the relative percentage of IsE-5-fraction was slightly greater than the percentage of tartrate resistant cells. In two patients with questionable HCL well marked IsE-5-fractions were recognized but no tartrate resistant cells. In one patient with HCL a relatively high percentage of tartrate resistant hairy-cells and in comparison an inadaquate low IsE-5-fraction was found. These different relations were explained with the more sensitive method of gelelectrophoresis and different affinity of substrates to AP.
Assuntos
Fosfatase Ácida/sangue , Isoenzimas/sangue , Leucemia de Células Pilosas/enzimologia , Leucemia Mieloide/enzimologia , Leucócitos/enzimologia , Doença Aguda , Plaquetas/enzimologia , Granulócitos/enzimologia , Humanos , Leucemia/enzimologia , Linfócitos/enzimologia , Macrófagos/enzimologiaRESUMO
Herpes simplex virus was grown in a 6-liter suspended culture of an atypical permanent human lymphoid cell line, Roswell Park Memorial Institute no. 8226. The kinetics of virus replication were determined by counting viruses by electron microscopy, plaque formation, and tissue culture infectivity. Deoxyribonucleic acid-dependent deoxyribonucleic acid polymerase activity was determined during the course of infection. Electron microscopy studies substantiated the kinetics of the virus infection in lymphoid cells.
Assuntos
Simplexvirus/crescimento & desenvolvimento , Replicação Viral , Contagem de Células , Linhagem Celular , Sistema Livre de Células , Células Cultivadas/enzimologia , Células Cultivadas/microbiologia , Meios de Cultura , Efeito Citopatogênico Viral , DNA Nucleotidiltransferases/metabolismo , Congelamento , Humanos , Pulmão , Melanoma , Microscopia Eletrônica , Simplexvirus/isolamento & purificação , Coloração e Rotulagem , Nucleotídeos de Timina/metabolismo , Trítio , Cultura de VírusRESUMO
The penetration of 12 commonly used anticancer agents through the blood-brain barrier (BBB) was measured in a rat model using a single-injection tissue-sampling technique. Two of the tested drugs penetrated the barrier, but only to a limited extent. Entry of the drugs into the brain tissue critically depends on molecular weight and lipophilia of the respective test compound. For drugs with a molecular weight of less than 500, BBB simply behaves like an oil/water interphase, whereas drugs with a molecular weight greater than 500 are practically excluded from transport through the BBB even if they show a favourable oil/water partition coefficient. However, permeability of cytostatics was strongly increased if short chain alkylglycerols, up to final concentrations of about 0.3 mol/l were added to the injected solution. Under these conditions the Brain-Uptake-Index (BUI) reached values up to about 50% (cyclophosphamide), depending on lipid solubility and molecular dimension of the respective test compound and the alkyl chain length of the glycerol derivative.
Assuntos
Antineoplásicos/metabolismo , Barreira Hematoencefálica , Éteres Fosfolipídicos , Animais , Antraquinonas/metabolismo , Disponibilidade Biológica , Bleomicina/metabolismo , Encéfalo/irrigação sanguínea , Butanóis/metabolismo , Permeabilidade Capilar , Radioisótopos de Carbono , Diglicerídeos/metabolismo , Doxorrubicina/metabolismo , Lisofosfatidilcolinas/metabolismo , Metotrexato/metabolismo , Mitoxantrona , Ratos , TrítioRESUMO
30 patients with advanced squamous cell carcinoma of the head and neck received initial chemotherapy with Cisplatin (100 mg/m2 i.v. day 1) and 5-Fluorouracil (1000 mg/m2 as 24-hour-infusion day 2-6). 1 patient reached complete remission, 16 patients presented a partial remission, 11 patients showed little response and 2 patients had progressive disease. Following chemotherapy, 29 patients were referred to surgery and/or irradiation. 16 patients received radical surgery. The surgical specimen of 5 patients had no histological evidence of cancer. Objective and subjective side effects of chemotherapy were serious and some patients refused further treatment or were rejected. The results were compared with the data from the literature. The considerably better results from Decker and Weaver et al. were partially explained by an overestimation of remission quality by clinical evaluation and by more therapy courses. At this time, there is no evidence of any benefit from chemotherapy, because there is no data on relapse free survival and over all survival. The position of chemotherapy in the multimodality treatment programme of head and neck cancer still needs to be discussed further.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Esquema de Medicação , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Concentrations of platin were determined with the method of atomic absorption spectroscopy in plasma and urine from the 1st until 28th day after cis-DDP (3 mg/kg) infusion for 1, 8, and 24 h. Maximum of plasma concentration was measured always at the end of the application time. Minimal concentration was 1.9 micrograms/ml, maximal concentration 5.8 micrograms/ml. Platin could be detected until the 21st respectively 28th day between 0.01 and 0.9 micrograms/ml. The duration of cis-DDP infusions was without influence on the mean excretion of platin. Between 24 and 25% of the infused platin was excreted after 24 h, between 4.8 and 7% after further 24 h, between 1 and 2% between the 3rd and 21st day, and less than 1% thereafter. Difference in pattern of toxicity could not be clearly detected.
Assuntos
Cisplatino/uso terapêutico , Platina/metabolismo , Adulto , Carcinoma de Células Escamosas/tratamento farmacológico , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Infusões Parenterais , Cinética , Neoplasias Pulmonares/tratamento farmacológico , Linfoma/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Platina/sangue , Platina/urina , Neoplasias Testiculares/tratamento farmacológicoRESUMO
The preliminary results of a controlled study for treatment of 33 patients with squamous cell carcinoma of the head and neck region with regimen A: cis-DDP (3 mg/M2 dl) plus Bleomycin (15 mg/m2 i.v. continuously d2-6) against regimen B: Methotrexate (30 mg/m2 i.v. dl + 6) and vindesine (3 mg/m2 i.v. dl + 7) were as follows: complete remission (cr): 1 X A, 0 X B; partial remission (pr): 6 X A, 4 X B; minor response (mr): 3 X A, 7 X B; no change (nc): 2 X A, 0 X B; progression (pg): 5 X A, 5 X B. Due to progressive disease 8 patients were further treated with the alternative regimen with following results: cr: 1 X A; mr: 1 X A, 2 X B; nc: 1 X B; pg: 3 X A. Considering prognostic factors it could be demonstrated that primary chemotherapy (pc) was more effective that applied after operation and/or radiotherapy (secondary chemotherapy = sc): cr + pr: (= 53%), 4 X sc (= 22%); nc + pg: 1 X pc (= 7%), 7 X sc (= 39%).
Assuntos
Antineoplásicos/uso terapêutico , Bleomicina/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Metotrexato/uso terapêutico , Vimblastina/análogos & derivados , Adulto , Idoso , Antineoplásicos/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vimblastina/uso terapêutico , VindesinaRESUMO
Treatment of patients with advanced squamous head and neck tumors demonstrates even with best surgical and x-ray techniques only five year survival rats between 10 and 30%. Chemotherapy in addition seems to improve these results. From July 79 to January 80 21 patients with advanced squamous-cell carcinoma at the head and neck region were treated in a controlled pilot study with Cisplatinum/Bleomycin or Methotrexate/vindesine. 6 patients were primarily treated with chemotherapy, all other secondary progressive disease after surgical and x-ray procedure. Without respect to the generally cell tolerated therapy modality on overall remission induction rate of 50 and 70% was observed. In a subsequent randomized controlled multicentric study both regimes will be compared concerning remission, survival and toxicity.