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1.
Appl Opt ; 53(26): 5934-43, 2014 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-25321674

RESUMO

Over the past 60 years, ground-based remote sensing measurements of the Earth's mesospheric temperature have been performed using the nighttime hydroxyl (OH) emission, which originates at an altitude of ∼87 km. Several types of instruments have been employed to date: spectrometers, Fabry-Perot or Michelson interferometers, scanning-radiometers, and more recently temperature mappers. Most of them measure the mesospheric temperature in a few sample directions and/or with a limited temporal resolution, restricting their research capabilities to the investigation of larger-scale perturbations such as inertial waves, tides, or planetary waves. The Advanced Mesospheric Temperature Mapper (AMTM) is a novel infrared digital imaging system that measures selected emission lines in the mesospheric OH (3,1) band (at ∼1.5 µm) to create intensity and temperature maps of the mesosphere around 87 km. The data are obtained with an unprecedented spatial (∼0.5 km) and temporal (typically 30″) resolution over a large 120° field of view, allowing detailed measurements of wave propagation and dissipation at the ∼87 km level, even in the presence of strong aurora or under full moon conditions. This paper describes the AMTM characteristics, compares measured temperatures with values obtained by a collocated Na lidar instrument, and presents several examples of temperature maps and nightly keogram representations to illustrate the excellent capabilities of this new instrument.

2.
J Clin Oncol ; 12(1): 97-106, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8270990

RESUMO

PURPOSE: Recombinant human macrophage colony-stimulating factor (rM-CSF) has been demonstrated to control the growth, differentiation, and function of mononuclear phagocytes. Preclinical studies have indicated antitumor effects, and therefore a phase I trial of rM-CSF in patients with malignancy was initiated. The toxicity and hematologic and immunologic effects were investigated. PATIENTS AND METHODS: rM-CSF was administered as a subcutaneous injection on days 1 through 5 and 8 through 12. Cycles were repeated every 28 days. Cohorts of four to seven patients received rM-CSF at dose levels from 0.1 to 25.6 mg/m2/d. Forty-two patients received 88 cycles of rM-CSF. All patients had metastatic solid tumors refractory to standard therapy. RESULTS: The toxicity of rM-CSF was mild. Dose-limiting toxicity included thrombocytopenia (two patients) and iritis (one patient) occurring at a dose of 25.6 mg/m2/d. Hematologic studies demonstrated dose-related monocytosis occurring routinely at doses > or = 3.2 mg/m2/d, and thrombocytopenia. Immunologic studies demonstrated enhanced secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) by monocytes after in vitro stimulation with lipopolysaccharide, and increased expression of TNF-alpha mRNA at higher rM-CSF dose levels. Pharmacokinetic studies demonstrated that the systemic clearance rate of M-CSF increases during week 1 of therapy, resulting in lower blood levels of M-CSF during the second week of therapy. CONCLUSION: rM-CSF can be safely administered to patients, and has biologic activity on peripheral-blood monocytes.


Assuntos
Fator Estimulador de Colônias de Macrófagos/uso terapêutico , Monócitos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Adulto , Idoso , Citocinas/biossíntese , Citocinas/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Injeções Subcutâneas , Fator Estimulador de Colônias de Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Macrófagos/efeitos adversos , Fator Estimulador de Colônias de Macrófagos/farmacocinética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Monócitos/imunologia , Neoplasias/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico
3.
Genetics ; 121(3): 539-50, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2714638

RESUMO

A restriction map was constructed of the ribosomal cistron in a mosquito, Aedes albopictus (Skuse). The 18s, 28s and nontranscribed spacer (NTS) regions were subcloned and used to probe for intraspecific variation. Seventeen populations were examined throughout the world range of the species. No variation was detected in the coding regions but extensive and continuous variation existed in the NTS. The NTS consisted of two nonhomologous regions. The first region contained multiple 190-bp AluI repeats nested within larger XhoI repeats of various sizes. There was a large number of length variants in the AluI repeat region of the NTS. No repeats were found in the second region and it gave rise to relatively fewer variants. An analysis of NTS diversity in individual mosquitoes indicated that most of the diversity arose at the population level. Discriminant analysis was performed on spacer types in individual mosquitoes and demonstrated that individuals within a population carried a unique set of spacers. In contrast with studies of the NTS in Drosophila populations, there seems to be little conservation of spacers in a population. The importance of molecular drive relative to drift and selection in the generation of local population differentiation is discussed.


Assuntos
Aedes/genética , DNA Ribossômico/genética , Genes , Variação Genética , Animais , Brasil , DNA/genética , DNA/isolamento & purificação , Immunoblotting , Isoenzimas/genética , Família Multigênica , Hibridização de Ácido Nucleico , Mapeamento por Restrição , Especificidade da Espécie , Estados Unidos
4.
Clin Cancer Res ; 5(10): 2780-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10537342

RESUMO

Interleukin 12 (IL-12) is known to play an important role in the development of an antitumor response. Its activity has been shown to be dependent upon the intermediate production of IFN-gamma and the influx into the tumor of CD8 lymphocytes. In a murine model, tumor regression induced by IL-12 treatment correlated with IFN-gamma, IP-10, and Mig expression in the tumor bed and was abrogated by antibodies to both chemokines. Here we examined the effects of rHuIL-12 on IFN-gamma and CXC chemokine gene expression in patients with renal cell carcinoma (RCC) in an attempt to determine whether a similar series of molecular events leading to IL-12-mediated tumor regression in mice is also detectable in humans. As in the murine RENCA model, cultured RCC cells themselves could be induced by IFN-gamma to synthesize IP-10 and Mig mRNA. Explanted RCC produced IFN-gamma and IP-10 mRNA in response to IL-12 treatment, which was consistent with the finding that biopsied RCC tumors from IL-12-treated patients also variably expressed augmented levels of those molecules after therapy. Although Mig mRNA was present in the majority of biopsied tumors prior to treatment, both the Mig and IP-10 chemokines as well as IFN-gamma were induced in the peripheral blood mononuclear cells of IL-12-treated patients. Skin biopsies of IL-12-treated patients also all synthesized IP-10 mRNA. This study demonstrates that recombinant human IL-12 therapy of patients with RCC has the potential to induce the expression of gene products within the tumor bed that may contribute to the development of a successful antitumor response.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Quimiocinas CXC/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular , Interferon gama/biossíntese , Interleucina-12/farmacologia , Neoplasias Renais/tratamento farmacológico , Animais , Quimiocina CXCL10 , Quimiocina CXCL9 , Quimiocinas CXC/genética , Humanos , Camundongos , RNA Mensageiro/análise , Proteínas Recombinantes/farmacologia , Células Tumorais Cultivadas
5.
Clin Cancer Res ; 4(10): 2337-47, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9796963

RESUMO

Studies have demonstrated abnormalities of the CD3/T-cell antigen receptor (TCR) and pathways of signal transduction in T lymphocytes from animals and patients with advanced malignancy. Diminished expression of TCRzeta and p56(lck) that are associated with the TCR and reduced nuclear localization of RelA containing nuclear factor kappaB (NFkappaB) complexes have been noted. These defects have been described in T cells from patients with malignant melanoma, renal cell carcinoma (RCC), ovarian cancer, and colorectal cancer. Preliminary observations also indicate possible correlation with clinical variables such as stage in selected instances. To further characterize altered expression of TCRzeta, p56(lck), and impaired activation of NFkappaB, T lymphocytes were obtained from 65 patients with RCC, the majority of whom were receiving combination cytokine therapy [interleukin (IL)-2, IFN alpha-containing regimens] and 37 control individuals. In 29 of these patients, levels of TCRzeta and p56(lck) were determined by Western blots of T-cell lysates and semiquantitated using densitometry. Relative levels were then correlated with a series of clinical variables including response to therapy, performance status, survival, disease sites, age, and others. In another group of 28 patients (three individuals from the first group), the frequency of abnormal NFkappaB activation was studied using electrophoretic mobility shift assays after activation of T cells with phorbol myristate acetate/ionomycin or anti-CD3 monoclonal antibody. Changes in these signaling molecules during cytokine treatment were also investigated. TCRzeta and p56(lck) were detected in the peripheral blood T cells in 27 of 29 patients, and overall, reduced levels were noted visually in 12 of 29 (41%) and 13 of 29 (45%) individuals, respectively. When levels were semiquantitated using densitometry, significant decreases of TCRzeta (P = 0.029) and p56(lck) (P = 0.029) but not CD3epsilon (P = 0.131), compared with control levels, were found. In patients treated with IL-2/IFN alpha-based therapy, relative levels of TCRzeta increased significantly (P = 0.002) on day 15 of cycle one compared with the baseline. Correlations of TCRzeta or p56(lck) levels with response or disease variables, except for lower TCRzeta levels (P < 0.001) in the presence of bone metastases, were not found. Abnormal NFkappaB activation after stimulation with phorbol myristate acetate/ionomycin and/or anti-CD3 monoclonal antibody was found in 59% of patients (17 of 28) and was not accounted for by the advanced age of the study cohort. Activation of NFkappaB in peripheral blood T cells was inducible during cytokine therapy in four of six individuals who displayed impaired NFkappaB activity prior to therapy. Moreover, impaired activation of NFkappaB does not appear linked to a reduction of TCRzeta expression, because in five patients, normal TCRzeta levels were present although kappaB binding was not inducible. In the majority of patients with advanced RCC, peripheral blood T cells express TCRzeta and p56(lck), and in a subset, reduced levels of these TCRzeta associated molecules are seen that may increase during cytokine-based therapy. Abnormal activation of NFkappaB is also present in >50% of patients and may also revert to normal during IL-2/IFN alpha-based treatment. This alteration in NFkappaB activation occurred in the presence of normal expression of TCRzeta-associated signaling elements. The clinical significance of these findings remains unclear.


Assuntos
Carcinoma de Células Renais/imunologia , Citocinas/uso terapêutico , Neoplasias Renais/imunologia , Transdução de Sinais , Linfócitos T/metabolismo , Carcinoma de Células Renais/terapia , Humanos , Neoplasias Renais/terapia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/análise , Proteínas de Membrana/análise , NF-kappa B/metabolismo , Receptores de Antígenos de Linfócitos T/análise
6.
Clin Cancer Res ; 4(3): 635-42, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9533531

RESUMO

Because tamoxifen and all-trans-retinoic acid (ATRA) have additive antitumor effects in preclinical systems, we performed a Phase I/II clinical trial of this combination in patients with advanced breast cancer. Patients with potentially hormone-responsive advanced breast cancer were enrolled. All received 20 mg of tamoxifen by mouth daily. Consecutive cohorts of 3-6 patients were treated on odd-numbered weeks with ATRA at doses of 70, 110, 150, 190, or 230 mg/m2/day. Twenty-six patients were entered in this trial; 25 were evaluable. A dose of 230 mg/m2 ATRA produced unacceptable headache and dermatological toxicity, but doses < or = 190 mg/m2 were tolerable. Two of 7 patients with measurable disease responded. Seven of 18 patients with evaluable, nonmeasurable disease achieved disease stability for more than 6 months. Plasma AUCs on day 1 of successive weeks of treatment were stable over time. A nonsignificant decrease in serum insulin-like growth factor I levels was noted during treatment, but this trend was similar to that observed in three "control" patients treated with tamoxifen alone. When given with daily tamoxifen, the maximum tolerated dose of ATRA that could be given on alternate weeks was 190 mg/m2/day. This schedule of ATRA resulted in repeated periods of exposure to potentially therapeutic concentrations of ATRA. Declines in the serum insulin-like growth factor I concentrations observed in patients treated with tamoxifen and ATRA were similar to those observed in patients treated with tamoxifen alone. Objective responses were observed, some in patients who had previously progressed while receiving tamoxifen, suggesting that further studies would be of interest.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/uso terapêutico , Tretinoína/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores/sangue , Neoplasias da Mama/patologia , Esquema de Medicação , Feminino , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos
7.
Clin Cancer Res ; 2(2): 347-57, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9816178

RESUMO

We conducted a Phase I trial of s.c. recombinant human interleukin 3 (rhIL-3) to evaluate the toxicity, maximal tolerated dose, pharmacokinetics, and in vivo biological effects of this cytokine. Thirty-one patients with refractory cancer were entered into the study between November 1991 and June 1993. Therapy consisted of s.c. rhIL-3 daily for 15 days administered to cohorts of three to nine patients at dose levels of 60-4000 microgram/m2/day. Cycles were repeated at intervals of 28 days. Seventy-five cycles of rhIL-3 were administered (median, two per patient) and the maximal tolerated dose was 2000 microgram/m2/day. Toxicity was moderate, with most patients developing chills, fever, and myalgia. Dose-limiting toxicity consisted of diarrhea (two patients) and headache (one patient). Hematological effects of rhIL-3 included significant dose-related increases of WBC (P < 0.001), neutrophils (P < 0.001), and eosinophils (P < 0.001). Platelet counts and absolute lymphocyte numbers also increased. Various CD3(+) lymphocyte subsets increased; however, lytic activity (natural killer and lymphokine-activated killer) of peripheral blood lymphocytes was not enhanced. Serum levels of the soluble IL-2 receptor increased in a dose-related fashion, and IL-2-induced lymphocyte proliferation also was increased variably. Pharmacokinetic studies were performed in 13 patients, and area under the curve and maximal concentration values increased with increasing rhIL-3 dose levels (P < 0.001) and correlated with maximal changes from baseline in WBC, neutrophils, and eosinophils. rhIL-3 antibodies were detected in 8% of patients by day 29 of cycle 1 but were not neutralizing. rhIL-3 is well tolerated when administered s.c. and has reproducible hematological and immunological effects. The pleiotropic effects of this cytokine on various in vivo biological parameters were demonstrated clearly. Further studies of its immunoregulatory effects are warranted.


Assuntos
Interleucina-3/efeitos adversos , Neoplasias/terapia , Adulto , Idoso , Contagem de Células Sanguíneas/efeitos dos fármacos , Feminino , Humanos , Injeções Subcutâneas , Interleucina-3/administração & dosagem , Interleucina-3/farmacocinética , Interleucina-6/sangue , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/imunologia , Receptores de Interleucina-2/análise , Proteínas Recombinantes/efeitos adversos
8.
Clin Cancer Res ; 6(1): 78-89, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10656435

RESUMO

Exisulind (sulindac sulfone; FGN-1), a metabolite of sulindac without known effects on prostaglandin synthesis, can promote apoptosis and inhibit tumorigenesis in preclinical systems. We performed a Phase I trial of this compound in patients with familial adenomatous polyposis (FAP) to examine the tolerability and safety of this drug in the cancer chemoprevention setting. Six patients each were treated with exisulind at doses of 200, 300, and 400 mg p.o. twice a day. Reversible hepatic dysfunction was noted in four of six patients treated at the 400-mg p.o., twice-a-day dose level, but in only one to two of six patients treated at each of the lower dose levels. The serum half-life of exisulind was 6-9 h; little drug accumulation was noted over time. A nonsignificant trend toward increased apoptosis in polyps was noted at the maximum tolerated dose, but no decrease in polyp numbers or significant effects on cellular proliferation was noted. After treatment, polyps tended to display a "halo" appearance grossly and mucinous differentiation histologically. The maximum safe dose of exisulind is 300 mg p.o. twice a day in patients with subtotal colectomies. Reversible hepatic dysfunction limits further dose escalation. A decrease in polyp numbers could not be demonstrated, but the trend toward increased apoptosis at the MTD and the observation of mucinous change histologically suggest that further investigation of drugs of this class might be warranted.


Assuntos
Polipose Adenomatosa do Colo/tratamento farmacológico , Antineoplásicos/efeitos adversos , Sulindaco/análogos & derivados , Polipose Adenomatosa do Colo/patologia , Administração Oral , Adolescente , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Apoptose , Feminino , Meia-Vida , Humanos , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Sulindaco/administração & dosagem , Sulindaco/efeitos adversos , Sulindaco/farmacocinética
9.
Eur J Cancer ; 29A(8): 1122-7, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8390844

RESUMO

Because WR-2721 reduces the toxicity of cisplatin and carboplatin in preclinical systems, we have treated 35 patients in a phase I study of WR-2721 and carboplatin. As the plasma half-life of WR-2721 is short relative to that of carboplatin, WR-2721 was administered in two divided doses. This schedule produced acceptable toxicity in 24 patients treated with carboplatin 400 mg/m2 and escalating doses of WR-2721. In the subsequent 11 patients, WR-2721 was fixed at 740 mg/m2/dose and the dose of carboplatin was escalated. With WR-2721, grade 3-4 thrombopenia (platelets < 50 x 10(9)/l) was produced in 4/5 patients treated with carboplatin 625 mg/m2 and in 1/6 patients treated with carboplatin 500 mg/m2. Carboplatin pharmacokinetic parameters in 4 patients were similar to those reported for carboplatin alone. These results suggest that WR-2721 might increase the maximum tolerated dose of carboplatin from 400 to 500 mg/m2.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Amifostina/administração & dosagem , Amifostina/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carboplatina/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neutropenia/induzido quimicamente , Platina/sangue , Trombocitopenia/induzido quimicamente
10.
Semin Oncol ; 26(2 Suppl 7): 41-50, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10348260

RESUMO

Thrombocytopenia is a significant problem for patients receiving prolonged or aggressive chemotherapy for malignancy. For carboplatin, it is the predominant dose-limiting toxicity and it is cumulative in nature. A number of agents have been evaluated for efficacy in reducing the problem of thrombocytopenia. Some have proved valueless and have been discarded. Others (eg, recombinant thrombopoietin) are under current study, and one (interleukin-11 or oprelvekin) is now commercially available. In addition, the currently available cytoprotectant, amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA), has been shown to reduce the severity and duration of thrombocytopenia caused by carboplatin. Because of the short half-life of amifostine relative to that of carboplatin, multiple doses of amifostine have been administered in conjunction with carboplatin. The optimal dosing regimen with amifostine and carboplatin needs to be further evaluated in clinical studies. Future trials will also expand these observations to carboplatin-containing combination chemotherapy regimens and will further define the role of amifostine as a multilineage bone marrow protectant. The ability of amifostine to demonstrate multilineage bone marrow protection differentiates it from currently available growth factors and fulfills a medical need, including reducing the need for platelet transfusions and maintaining the desired chemotherapy dose intensity.


Assuntos
Amifostina/uso terapêutico , Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Citoproteção , Substâncias Protetoras/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controle , Amifostina/administração & dosagem , Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Ensaios Clínicos como Assunto , Fatores Estimuladores de Colônias/uso terapêutico , Humanos , Transfusão de Plaquetas , Substâncias Protetoras/administração & dosagem , Trombopoetina/uso terapêutico
11.
J Thorac Cardiovasc Surg ; 106(2): 210-7, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8393505

RESUMO

To clarify the value of deoxyribonucleic acid (DNA) ploidy analysis, we prospectively studied single-parameter flow cytometric findings of fresh tissue from 272 patients with primary non-small-cell lung cancer from whom adequate tissue from the lung cancer was available. The mean age of the patients was 65.5 years; 65.8% were men. Histologic types were as follows: adenocarcinoma, 107 (39.3%); squamous cell, 100 (36.8%); large cell, 56 (20.6%); adenosquamous, 8 (2.9%); and giant cell, 1 (0.4%). Histologic grades were as follows: I (well differentiated), 15 (5.5%); II, 100 (36.8%); and III, 157 (57.7%). American Joint Committee on Cancer stages were as follows: I, 151 (55.5%); II, 38 (14%); III, 74 (27.2%); and IV, 9 (3.3%). Survivals at 1 year and 3 years were 74.2% +/- 2.8% and 52.4% +/- 4.8%, respectively. For non-squamous cell lung cancer, multivariate analyses with the Cox proportional hazards regression model for survival showed (1) that increasing American Joint Committee on Cancer stage (p < 0.001), male gender (p = 0.02), and histologic grades II and III (p = 0.04) were of independent (negative) prognostic significance and (2) that the presence and absence of DNA aneuploidy (p = 0.91), the classification of DNA histogram (p = 0.81), the DNA index (p = 0.46), and the results of cell cycle analysis in tumors with no aneuploidy (S phase, p = 0.23; S + G2M, p = 0.62) were of no prognostic significance. For squamous cell lung cancer, multivariate analyses showed that increasing American Joint Committee on Cancer stage (p = 0.003) and increasing DNA index (p = 0.009) were of independent (negative) prognostic significance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA de Neoplasias/análise , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Ploidias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
12.
J Cancer Res Clin Oncol ; 127(5): 319-24, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11355147

RESUMO

PURPOSE: A phase I followed by a phase II trial utilizing rIL-2, IFN alpha, and 5-FU were conducted in patients with unresectable and/or metastatic renal cell carcinoma. METHODS: Treatment consisted of: rIL-2 at 5.0 x 10(6) IU/m2 SQ on days 1-5 for 4 weeks, rHUIFN alpha-2a at 5.0 x 10(6) U/m2 SQ on days 1, 3, and 5 for 4 weeks, and 5-FU by IV bolus on days 1-5 during week 1. In the phase I study, patients were treated at varying doses of 5-FU: I-none, II-250 mg/m2, III-300, and IV 375. A phase II trial was then conducted utilizing the same schedule and maximum tolerated dose (MTD) for 5-FU. RESULTS: Twenty patients were entered into the phase I trial. Dose-limiting toxicity included grade III nausea and vomiting, and one sudden cardiac death. The MTD for 5-FU was determined to be 300 mg/m2. In the phase II trial, a median of two cycles of therapy was administered to 25 evaluable patients. Toxicity was moderate and consisted primarily of fevers, chills, fatigue, nausea/vomiting, and anorexia. Grade IV thrombocytopenia, consistent with ITP, developed in one patient each on the phase I and phase II trial. Seven partial responses were seen among 25 patients treated in the phase II trial for a 28% (CI 12-49%) response rate. CONCLUSIONS: The addition of 5-FU to rIL-2 and rHuIFN alpha-2a appears to increase the toxicity of this therapy. Randomized trials will be required to determine if efficacy is enhanced.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Fluoruracila/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Anorexia/induzido quimicamente , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/mortalidade , Calafrios/induzido quimicamente , Terapia Combinada , Morte Súbita Cardíaca/etiologia , Relação Dose-Resposta a Droga , Fadiga/induzido quimicamente , Feminino , Febre/induzido quimicamente , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Interleucina-2/administração & dosagem , Interleucina-2/efeitos adversos , Neoplasias Renais/mortalidade , Tábuas de Vida , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Vômito/induzido quimicamente
13.
J Cancer Res Clin Oncol ; 127(10): 619-24, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11599798

RESUMO

PURPOSE: Some limitations of effective therapy in multiple myeloma include the low growth fraction of the malignant plasma cells, multi-drug resistance, and the presence of other concurrent diseases in this patient population. A phase I study was conducted to evaluate the toxicity of granulocyte macrophage colony stimulating factor (GM-CSF) in myeloma patients as well as the potential effect on the plasma cell labeling index (PCLI). Relapsed patients with multiple myeloma were eligible. METHODS: The first phase of this trial assessed the toxicity (including the effect on disease progression) of escalating doses (125-500 microg/m2 SC, days 1-5) of GM-CSF, and the effects of this cytokine on PCLI. Patients whose PCLI doubled and increased to > or = 1.7% were treated with chemotherapy including cyclophosphamide, vincristine, prednisone, and GM-CSF. Twenty-two patients were enrolled. RESULTS: The toxicity of GM-CSF was mild, and no dose-limiting side effects were seen. Twenty-five percent of patients (5/20) achieved the target PCLI, and 4/5 proceeded to receive chemotherapy. No relationship of GM-CSF dose to increases of the PCLI was noted. All patients who received chemotherapy responded. CONCLUSIONS: GM-CSF has acceptable toxicity in patients with multiple myeloma and produced increases of PCLI in selected individuals. Further studies of GM-CSF alone or in combination with chemotherapy are indicated.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Injeções Intravenosas/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Alanina Transaminase/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aspartato Aminotransferases/sangue , Feminino , Humanos , Masculino , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Seleção de Pacientes , Proteínas Recombinantes
14.
J Cancer Res Clin Oncol ; 120(3): 169-72, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8263014

RESUMO

The use of intrapleural sclerosing agents to control reaccumulation of pleural fluid in patients with malignant effusions has been widely investigated. A phase I trial of intrapleural recombinant human interferon alpha (rHuIFN alpha 2b) was initiated to determine the toxicity and maximal tolerated dose in this group of patients. rHuIFN alpha 2b was instilled as a single dose following chest tube (15/16) or percutaneous (1/16) drainage of cytologically proven malignant effusions. Doses of rHuIFN alpha 2b were escalated from 25 x 10(6) to 200 x 10(6) U/m2 in cohorts of three to four patients. Toxicity was mild to moderate, and included chills, fever and chest pain, and resembled that produced by systemic administration of rHuIFN alpha 2b. Dose-limiting toxicity occurred at 200 x 10(6) U/m2 and consisted of hepatic enzyme elevations and renal failure. Partial control of the effusions was noted in two patients, with two additional patients having stable disease. Phase II trials of rHuIFN alpha 2b should utilize up to 150 x 10(6) U/m2 for intrapleural instillation.


Assuntos
Interferon-alfa/administração & dosagem , Derrame Pleural/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/complicações , Derrame Pleural/etiologia , Proteínas Recombinantes
15.
Cancer Chemother Pharmacol ; 46(3): 251-4, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11021744

RESUMO

PURPOSE: To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy. METHODS: PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days. Pharmacokinetic studies to determine PZA plasma concentrations were performed. RESULTS: No responses were seen in 14 response-evaluable patients. Patients received a median of two cycles of PZA (range 1-6). Toxicity included neutropenia and neurologic side-effects, which were > or = grade III in 73% and 14%, respectively. High plasma concentrations of PZA (Cmax) correlated with low neutrophil counts (P = 0.04). CONCLUSIONS: PZA is inactive at this dose and schedule in colorectal cancer, and produces moderately severe toxicity.


Assuntos
Acridinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Substâncias Intercalantes/uso terapêutico , Pirazóis/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Acridinas/efeitos adversos , Acridinas/farmacocinética , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Neoplasias do Colo/sangue , Feminino , Humanos , Substâncias Intercalantes/efeitos adversos , Substâncias Intercalantes/farmacocinética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Doenças do Sistema Nervoso/induzido quimicamente , Neutropenia/induzido quimicamente , Pirazóis/efeitos adversos , Pirazóis/farmacocinética , Neoplasias Retais/sangue
16.
Oecologia ; 48(3): 414-417, 1981 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28309761

RESUMO

Three hemipteran herbivores partition a common resource plant, Senecio smallii, on the basis of bud density and plant patch size. The monophagous herbivore, Neacoryphus bicrucis, is most abundant in larger patches where bud density is greatest. The oligophagous herbivore, Harmostes reflexulus, is most abundant in small patches of high bud density. The polyphagous species, Lygus pratensis, is most abundant in small patches where abundance is independent of bud density. The aggressive nature of the monophagous herbivore appears to mediate the responses of the other species.

17.
J Med Entomol ; 32(3): 353-60, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7616527

RESUMO

The base sequence of the internal transcribed spacer 1 (ITS 1) of ribosomal DNA of the tick Ixodes scapularis Say (= I. dammini Spielman, Clifford, Piesman & Corwin) was determined to assess genetic divergence between populations along the eastern (Atlantic) seaboard of the United States. Twenty sequences were obtained from localities down the eastern margin of the species's range: 10 from the southeast (Georgia and Florida), seven from the middle east (North Carolina, Maryland), and three from the northeast (Massachusetts, New Jersey, New York). Both the neighbor-joining and parsimony methods cluster most of the southeastern sequences together and most of the middle eastern sequences together but fail to cluster those from the northeast. In addition, an F ratio test revealed significant between-region sequence variation. Thus, there appears to be genetic structuring on at least a macrogeographic scale. Only 23% (SEM = 6.4%) of the sequence variation occurs between regions, with the vast majority of variation, 77% (SEM = 6.4%), being within region. These data, plus other published data, indicate that I. scapularis constitutes a single species. However, the pattern of variation is consistent with restricted gene flow between regions or, alternatively, with recent introgression between northern and southern types in the middle-eastern part of the species's range.


Assuntos
DNA Ribossômico/genética , Carrapatos/genética , Animais , Sequência de Bases , Variação Genética , Dados de Sequência Molecular , Filogenia , Carrapatos/classificação , Transcrição Gênica , Estados Unidos
18.
J Med Entomol ; 30(1): 54-63, 1993 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8433346

RESUMO

Reciprocal crosses between Ixodes dammini Spielman, Clifford, Piesman & Corwin from Massachusetts and Ixodes scapularis Say from Georgia produced offspring through the F3 generation when the experiment was discontinued. Reciprocal I. dammini x Ixodes pacificus Cooley & Kohls (California) and I. scapularis x I. pacificus crosses produced F1 progeny; however, all progeny were sterile. Assortative mating experiments between I. dammini and I. scapularis indicated that males and females of both species mated with the opposite sex of heterospecific or conspecific ticks when there was a choice. Conventional discriminant analysis of morphometric measurements of ticks from Georgia, North Carolina, Maryland, Massachusetts, and two populations of F1 hybrids indicated that there were recognizable differences. However, size-free (sheared) discriminant analysis indicated that these differences were largely size-dependent, with much overlap of the four eastern and two hybrid populations but no overlap with I. pacificus from California. Analysis of chromosomes (morphology and C band) indicated no differences between the Georgia and Massachusetts populations but showed a difference between them and the California population of I. pacificus. Analysis of isozymes showed that the genetic identity value for the Georgia and Massachusetts populations was within the normal range for conspecific populations, whereas the California population indicated congeneric but not conspecific relatedness to the Georgia and Massachusetts populations. Life cycle data collected under similar laboratory conditions showed no differences in length of feeding and molting periods among Georgia, Massachusetts, and California populations. These data and results of the work of other authors on tick host preferences and vector competence indicate that I. dammini is not a valid species separate from I. scapularis. Because the name Ixodes scapularis Say, 1821, has priority over the name Ixodes dammini Spielman, Clifford, Piesman & Corwin, 1979, I. dammini is relegated to a junior subjective synonym of I. scapularis (based on Article 23 of the International Code of Zoological Nomenclature).


Assuntos
Vetores Aracnídeos/classificação , Carrapatos/classificação , Animais , Cruzamentos Genéticos , Feminino , Hibridização Genética , Isoenzimas/análise , Doença de Lyme/transmissão , Masculino
19.
Clin Sports Med ; 2(3): 563-70, 1983 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-6652704

RESUMO

The life of the artist who devotes himself or herself to dance as a career can be divided into seven stages. Each stage seems to have specific physical problems and challenges as well as success in technical and artistic achievement.


Assuntos
Envelhecimento , Arte , Dança , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aptidão Física , Competência Profissional
20.
Acad Manage J ; 38(6): 1726-43, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10169684

RESUMO

The subjective experience of workplace health and safety risk among exposed individuals is little understood. Health and safety risks are associated with multifaceted subjective interpretations different from those associated with other elements of the work environment and more directly influential on work attitudes and behavior than actual risk. This article conceptually and operationally defines these interpretations and evidences the influence of chronic risk exposure on job satisfaction, stress, and distraction from work tasks.


Assuntos
Emprego , Saúde Ocupacional , Gestão de Riscos , Assunção de Riscos , Adulto , Emprego/psicologia , Feminino , Previsões , Humanos , Satisfação no Emprego , Masculino , Cultura Organizacional , Inquéritos e Questionários , Estados Unidos
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