RESUMO
Sialyl transferase activity was demonstrated on the surfaces of intact, cultured lymphoblastoid cells (RAJI) derived from a Burkitt's lymphoma. Pretreatment of the cells with neuraminidase increased the labeled sialoprotein by severalfold. A nunber of nucleotides were effective in decreasing the amount of sialoprotein assembly. CMP was the most effective inhibitor. UMP, AMP, and GMP were also inhibitory, but to a lesser degree. The diphosphate derivatives were similarly inhibitory, but generally less active than their monophosphate counterparts. The cyclic nucleotides were the least effective of all nucleotides tested; cCMP and cAMP showed a small degree of activity, whereas cUMP and cGMP were without effect. These studies indicated that a number of noncyclic and cyclic nucleotides can influence the activity of the sialyl transferase system.
Assuntos
Linfoma de Burkitt/enzimologia , Nucleotídeos/farmacologia , Sialiltransferases/antagonistas & inibidores , Transferases/antagonistas & inibidores , Monofosfato de Adenosina/farmacologia , Linfoma de Burkitt/metabolismo , Membrana Celular/enzimologia , Células Cultivadas , AMP Cíclico/farmacologia , GMP Cíclico/farmacologia , Monofosfato de Citidina/farmacologia , Nucleotídeos de Guanina/farmacologia , Proteínas de Neoplasias/biossíntese , Nucleotídeos Cíclicos/farmacologia , Sialoglicoproteínas/biossíntese , Nucleotídeos de Uracila/farmacologiaAssuntos
Neoplasias/complicações , Sepse/complicações , Infecções Estafilocócicas/complicações , Infecções Estreptocócicas/complicações , Adulto , Idoso , Infecção Hospitalar/complicações , Infecção Hospitalar/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/complicações , Prognóstico , Sepse/diagnóstico , Sepse/etiologiaRESUMO
Ganglioneuroblastoma is a rare neoplasm of adults. Some information about the natural history and response to therapy can be obtained from two cases seen recently at our hospital and 17 cases in the literature. These tumors occur in adults of any age and are usually located in the retroperitoneum, mediastinum, or neck. Evidence of the tumor may be present years before diagnosis. Elevations of urinary catecholamines were documented in three cases and the levels correlated with progression or resection of the neoplasm. The tumor spreads either by local invasion or distant metastasis. Attempts at radiotherapy and chemotherapy in the treatment of unresectable or disseminated tumor has not resulted in objective improvement. This contrasts with the widely reported objective successes and cures of ganglioneuroblastomas occurring in childhood. Surgical excision of localized disease was the only curative therapeutic modality in the cases we reviewed.
Assuntos
Ganglioneuroma , Adulto , Idoso , Feminino , Ganglioneuroma/epidemiologia , Ganglioneuroma/patologia , Ganglioneuroma/terapia , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Masculino , Neoplasias do Mediastino/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retroperitoneais/epidemiologiaRESUMO
A quantitative, enzyme-linked immunoadsorbent assay has been developed for the simian virus 40 large T antigen. When hamster anti-simian virus 40 tumor serum was used, this method permitted specific identification of large T antigen and its analog, the D2 hybrid protein, a molecule with the same C-terminal approximately 600 amino acids as large T antigen. The sensitivity limit of this test was 0.63 ng of protein. The slopes of the regression lines of the enzyme-linked immunosorbent assay titrations performed with highly purified D2 or simian virus 40 large T antigen and with crude extracts of simian virus 40-infected monkey and transformed human cells were identical. Thus, the curve generated with a purified protein, such as D2, can serve as a quantitative standard for the measurement of large T antigen in a wide variety of extracts. Furthermore, solutions containing high salt concentrations and buffers containing up to 0.1% Nonidet P-40 did not interfere with the assay, making it applicable to the measurement of large T antigen in a variety of chromatographic fractions. The enzyme-linked immunosorbent assay was three times more sensitive, was significantly faster to perform, and was quantitatively valid over a much broader large-T-antigen concentration range than the complement fixation test. As such, it should be useful in future studies of the structure and function of this protein.
Assuntos
Antígenos de Neoplasias/análise , Antígenos Virais/análise , Polietilenoglicóis , Vírus 40 dos Símios/imunologia , Sulfato de Amônio/farmacologia , Antígenos Virais de Tumores , Linhagem Celular , Transformação Celular Neoplásica , Transformação Celular Viral , Testes de Fixação de Complemento , Detergentes/farmacologia , Ensaio de Imunoadsorção Enzimática , Glicerol/farmacologia , Octoxinol , Cloreto de Sódio/farmacologiaRESUMO
Sixteen patients with metastatic melanoma entered this phase II study of the efficacy of monthly cycles of Bisantrene. Toxicity was characterized by leukopenia, resulting in the hospitalization of one patient for a febrile incident, and superficial phlebitis. The results were similar to those of previous studies, in that among the 13 patients evaluable for response (six previously untreated with chemotherapy) there were no responses.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Melanoma/secundário , Adulto , Idoso , Antracenos/administração & dosagem , Antracenos/efeitos adversos , Antracenos/uso terapêutico , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Humanos , Illinois , Infusões Intravenosas , Leucopenia/induzido quimicamente , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Flebite/induzido quimicamente , Taxa de SobrevidaRESUMO
We have conducted a phase II trial of fludarabine phosphate for advanced measurable adenocarcinoma of the pancreas. The drug was administered every 4 weeks by a daily-times-5 bolus schedule beginning at 20 mg/m2/day. No responses were observed in 20 evaluable patients, 18 of whom were previously untreated. Dose-limiting toxicity was leukopenia, and gastroenterologic side effects were frequent. Life-threatening or fatal renal dysfunction occurred in 3 patients. In this schedule fludarabine phosphate is ineffective against adenocarcinoma of the pancreas and appears to have unpredictable severe renal toxicity.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Fosfato de Vidarabina/análogos & derivados , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Fosfato de Vidarabina/efeitos adversos , Fosfato de Vidarabina/uso terapêuticoRESUMO
A phase II trial of 4' Deoxydoxorubicin (DXDX) was conducted in unresectable previously untreated non-small cell lung cancer patients. DXDX was administered every 3 weeks by short intravenous infusion at a starting dose of 30 mg/m2, with dose escalation to 40 mg/m2 toxicity permitting. Four responses, all partial, were observed in 35 evaluable patients, for a response rate of 11% (95% confidence limits 3.2% and 26.7%). Myelosuppression was the dose-limiting toxicity. Cardiotoxicity was not seen. DXDX has minimal activity against non-small cell lung cancer as a single agent at the dosage used in this study.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Carcinoma Broncogênico/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doxorrubicina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Avaliação de Medicamentos , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como AssuntoRESUMO
In an Illinois Cancer Center phase II trial, fludarabine phosphate was administered to a total of 14 patients (9 men, 5 women) with advanced, measurable, gastric adenocarcinoma. Fludarabine phosphate was given as a rapid intravenous (IV) bolus at a starting dose of 20 mg/m2/d for the first 5 days of a 28-day cycle. For subsequent cycles, the dose was escalated in increments of 2 mg/m2/d, provided that no toxicities greater than grade 1 were noted. In cases of grade 3 toxicity, dose reductions of 2 mg/m2/d were required, and patients who experienced grade 4 toxicities were removed from study. Receiving one complete 5-day course of fludarabine phosphate and surviving for 4 weeks on study were required for a patient to be evaluable for response. None of the patients responded to treatment. Although fludarabine phosphate was ineffective against gastric adenocarcinoma in this study, toxicity was acceptable at the 20 mg/m2/d times 5 every 28 days dose and schedule.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Fosfato de Vidarabina/análogos & derivados , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Fosfato de Vidarabina/administração & dosagem , Fosfato de Vidarabina/efeitos adversos , Fosfato de Vidarabina/uso terapêuticoRESUMO
Fludarabine Phosphate (FP), the 2-fluoro, 5'phosphate derivative of adenosine arabinoside (ara-A), was studied in 18 patients with advanced renal cell carcinoma. These patients had measurable disease and had not received chemotherapy. FP was administered at a loading dose of 20 mg/m2 followed by a 48-hour infusion at 30 mg/m2/day given every 21 days. There were no complete or partial responses seen. Toxicity was mainly hematologic, with leukopenia most commonly observed. FP given in this manner had no activity in advanced renal cell carcinoma.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Arabinonucleotídeos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Fosfato de Vidarabina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfato de Vidarabina/efeitos adversos , Fosfato de Vidarabina/análogos & derivadosRESUMO
Amonafide (nafidimide), a synthetic organic compound with an inhibitory effect on cellular replication, was used in a phase II study conducted by the Illinois Cancer Center in order to assess its efficacy and toxicity in advanced or recurrent squamous cell cancer of the head and neck. Eligible patients had received no more than one prior adjuvant or neoadjuvant chemotherapy, had normal bone marrow, renal and hepatic function, ECOG performance status of 0-2, and bidimensionally measurable disease. Eligible patients were administered amonafide at a starting dose of 300 mg/m2 for five consecutive days every 3 weeks with dose escalation or de-escalation according to established hematologic criteria in the absence of disease progression. Nineteen of 22 entered patients were evaluable for response and all patients were evaluable for toxicity. Eleven of 19 patients achieved stable disease. Median time to progression after start of treatment was 57 days, for the 18 patients for whom the date of progression is known. There were no partial or complete responses. Hematologic toxicity was dose limiting with grade 3-4 neutropenia in 50 percent of patients and 4 deaths associated with neutropenic sepsis. Non-hematologic toxicity was mild to moderate with nausea and vomiting predominating. In this study, amonafide was a myelotoxic, inactive treatment in advanced/recurrent head and neck cancer. Further use in head and neck cancer appears unwarranted.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Imidas/uso terapêutico , Isoquinolinas/uso terapêutico , Adenina , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/secundário , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imidas/efeitos adversos , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Naftalimidas , Organofosfonatos , Resultado do TratamentoRESUMO
Echinomycin, a cyclic peptide in the family of quinoxaline antibiotics, was evaluated in patient with metastatic, soft tissue sarcoma not previously treated for metastatic disease. The starting dose of echinomycin was 1,200 mcg/m2 administered intravenously, once weekly x 4, followed by a two-week break. The protocol design called for dose escalation on subsequent cycles of therapy, but because of significant toxicity, dose escalation occurred in only 5 of 25 treatment cycles. Severe nausea and vomiting was the most common toxicity. No clinical responses were observed in the 12 evaluable patients. Echinomycin at this dose and schedule is inactive in metastatic soft tissue sarcoma.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Drogas em Investigação/uso terapêutico , Equinomicina/uso terapêutico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversos , Equinomicina/administração & dosagem , Equinomicina/efeitos adversos , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sarcoma/mortalidade , Sarcoma/secundário , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologiaRESUMO
Twelve patients with recurrent, metastatic, or inoperable gastric adenocarcinoma were enrolled in an Illinois Cancer Center phase II trial of amonafide (nafidimide), a novel compound that acts as a DNA intercalator. Treatment consisted of a 60-minute infusion of amonafide which was administered daily for 5 consecutive days every 3 weeks at a starting dose of 300 mg/m2/d. Doses were modified according to the grade of toxicity experienced and eight patients underwent dose escalations. All 12 patients were evaluable for response and toxicities were predominantly hematologic. Stabilization of disease for at least 28 days was observed in seven patients and disease progression was noted in five. The median survival was 7.4 months. Doses were sufficient to produce severe bone marrow toxicity in one-third of the patients treated. None of the patients responded to therapy, implying a true response rate less than .221. Based on the results of this study, amonafide showed no activity against gastric adenocarcinoma; however toxicity appeared acceptable at the 300 mg/m2/d x 5 consecutive days every 3 weeks dose and schedule.