RESUMEN
The primary end point of the study was the analysis of associations between polymorphisms with putative influence on 5-fluorouracil/irinotecan activity and progression-free survival (PFS) of patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. Peripheral blood samples from 146 prospectively enrolled patients were used for genotyping polymorphisms in thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), excision repair cross-complementation group-1 (ERCC 1) xeroderma pigmentosum group-D (XPD), X-ray cross-complementing-1 (XRCC 1), X-ray cross-complementing-3 (XRCC 3) and uridine diphosphate-glucuronosyltransferases-A1 (UGT1 A1). TS 3'-UTR 6+/6+ and XRCC3-241 C/C genotypes were associated with adverse PFS. Hazard ratio for PFS achieved 2.89 (95% confidence interval=1.56-5.80; P=0.002) in 30 patients (20%) with both risk genotypes. Risk for Grade III-IV neutropenia was significantly associated with UGT1A1*28 7/7 genotype. These promising findings deserve further investigations and their validation in independent prospective studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Perfilación de la Expresión Génica/métodos , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Camptotecina/análogos & derivados , Camptotecina/farmacología , Camptotecina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Genotipo , Humanos , Irinotecán , Leucovorina/farmacología , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Farmacogenética/métodos , Polimorfismo Genético/efectos de los fármacos , Polimorfismo Genético/genética , Estudios ProspectivosRESUMEN
PURPOSE: To evaluate the effect of the anti-cancer drug carboplatin on plasma concentrations and urinary excretion of L-carnitine (LC) and its main ester, acetyl-L-carnitine (ALC), in cancer patients. METHODS: Plasma and urine concentrations of LC and ALC from 11 patients on carboplatin therapy (1 h intravenous infusion; AUC dose 4.8 +/- 1.1 mg/ml min) in combination with docetaxel, paclitaxel or vinorelbine, were determined by high-performance liquid chromatography with fluorimetric detection. RESULTS: Before carboplatin therapy, the mean +/- SD plasma concentrations of LC and ALC were 47.8 +/- 10.9 and 7.04 +/- 1.04 nmoles/ml, respectively, and remained constant throughout the entire study period. In contrast, urinary excretion of LC and ALC, increased significantly during the chemotherapy from 115 +/- 105 to 480 +/- 348 micromoles/day (P < 0.01) and from 41 +/- 41 to 89 +/- 52 micromoles/day (P < 0.05) for LC and ALC, respectively, subsequently reverting to normal 6 days after the end of chemotherapy. Similarly, the renal clearance of LC and ALC increased substantially during chemotherapy from 1.67 +/- 1.43 to 9.05 +/- 9.52 ml/min (P < 0.05) and from 4.02 +/- 4.51 to 7.97 +/- 5.05 ml/min (P = not significant) for LC and ALC, respectively, reverting to normal 6 days after the end of chemotherapy. Plasma concentrations and urinary excretion of glucose, phosphate and urea nitrogen and creatinine clearance, however, were not affected by carboplatin therapy, indicating no impaired kidney function. CONCLUSION: Treatment with carboplatin was associated with a marked urinary loss of LC and ALC, most likely due to inhibition of carnitine reabsorption in the kidney.
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Acetilcarnitina/orina , Carboplatino/uso terapéutico , Carnitina/orina , Neoplasias/tratamiento farmacológico , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Área Bajo la Curva , Carboplatino/administración & dosificación , Carboplatino/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Creatinina/orina , Docetaxel , Femenino , Glucosa/metabolismo , Humanos , Infusiones Intravenosas , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Neoplasias/orina , Paclitaxel/administración & dosificación , Fosfatos/orina , Taxoides/administración & dosificación , Urea/orina , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
BACKGROUND: The proportion of elderly within the general population is increasing and the incidence of colorectal cancer increases with age. Oxaliplatin and 5-fluorouracil (FU) combination is active in this disease. PATIENTS AND METHODS: This multicenter phase II study was designed to investigate feasibility, efficacy, activity of daily living (ADL) and instrumental activity of daily living (IADL) in elderly patients with metastatic colorectal cancer treated, as first-line chemotherapy, with a bi-fractionated oxaliplatin/5-FU based regimen. Treatment was oxaliplatin 45 mg/m2, leucovorin 200 mg/m2, 5-FU 400 mg/m2 and 22 h continuous infusion of 5-FU 600 mg/m2, all given intravenously on days 1 and 2, every 2 weeks. RESULTS: Seventy-eight patients were enrolled; median age was 75 years (range 70-85). Among 77 evaluable patients, we observed seven complete responses and 32 partial responses, for an overall response rate of 51% (95% confidence interval 40% to 62%). A stabilization of disease was observed in 25% of patients while 19 patients progressed. Canadian NCI grade 3/4 toxicities were: neutropenia in 32% of patients (febrile in two), diarrhea in 10%, mucositis in 4%, and fatigue in 4%. Sensory neuropathy was mild and occurred as grade 3 in 6% of patients. ADL and IADL scores did not change significantly during treatment. CONCLUSIONS: The bi-fractionated delivery of oxaliplatin plus 5-FU/leucovorin demonstrated high antitumor activity in elderly patients with advanced colorectal cancer. Splitting oxaliplatin administration might reduce incidence of severe neuropathy, although this has to be confirmed by further studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Resultado del TratamientoRESUMEN
BACKGROUND: The doxorubicin-docetaxel combination is active in breast cancer; the aim of the present study was to evaluate the complete response rate and safety profile of the doxorubicin and docetaxel regimen as first-line chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: Forty-three patients entered the study. Treatment plan was: doxorubicin (50 mg/m2, i.v. bolus) followed 1 hour later by docetaxel (75 mg/m2 i.v. infusion over 1 hour), q 3 weeks, for up to six courses. The patients achieving a response or a stabilisation of disease after 6 courses were allowed to intensify the treatment with docetaxel (100 mg/m2, q 3 weeks) for up to 2 courses. G-CSF (or GM-CSF) was administered if clinically indicated. RESULTS: Patients' median age was 57years (range 32-75) and 72% of them had visceral disease. A total of 217 doxorubicin-docetaxel courses were delivered, with 70% of patients receiving all the 6 planned cycles. Among the 40 patients assessable for response (WHO criteria), 7 (16%) achieved a complete remission and 22 (51%) a partial remission, for an overall response rate (intent-to-treat) of 67% (95% C.I. =53% to 81%). In 19 patients, the treatment was intensified with two more single-agent docetaxel cycles, without ameliorating the response. Twenty-seven patients with oestrogen receptor-positive received hormonal therapy as 'maintenance' after completing chemotherapy treatment. NCIC G3-G4 neutropenia was recorded in 58% of patients, with G/GM-CSF used in 23 (53%) patients and 91 (38%) cycles. No patients experienced severe cardiac or neurological toxicity. No toxic death occurred. With a median follow-up of 41 months among alive patients, we observed in responder patients an overall median time to progression and survival of 18 and 33 months respectively, with ten long-survivors still alive. CONCLUSION: This study confirmed the combination doxorubicin-docetaxel as a very active regimen for metastatic breast cancer. Remarkably long survival times were observed not only in complete responders, but also in those patients who responded partially. This might be equally attributed to first-line treatment and sequential maintenance hormonal therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Docetaxel , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Tasa de Supervivencia , Taxoides/administración & dosificación , Taxoides/efectos adversosRESUMEN
OBJECTIVES: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly. We studied the toxicity and efficacy of a weekly schedule of gemcitabine and cisplatin in elderly patients with advanced NSCLC. METHODS: Patients aged 70 years or above with advanced NSCLC were treated in a phase II prospective trial with gemcitabine 1,000 mg/m(2) and cisplatin 35 mg/m(2) on days 1, 8 and 15 every 28 days. RESULTS: Forty-eight patients with a median age of 74 years (range 70-78) participated in the study. We observed 14 cases with partial response, 14 with stable disease and 16 with progressive disease, whilst 4 patients were not evaluable. By intention-to-treat analysis, partial response rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9 months; 1-year survival probability was 34.4% and median time to progression was 4 months. Grade III-IV leukopenia was observed in 5/48 patients (10.4%), 20/48 patients (41.7%) had grade III-IV thrombocytopenia and 7/48 patients (14.6%) had grade III-IV anemia. One patient experienced grade III emesis and 2 patients had grade III-IV fatigue. CONCLUSIONS: At this dose and schedule the combination of gemcitabine and cisplatin appears to be an active and well-tolerated regimen for elderly patients with advanced NSCLC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Dosis Máxima Tolerada , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Resultado del Tratamiento , GemcitabinaAsunto(s)
Carcinoma de Células en Anillo de Sello/diagnóstico , Neoplasias Intestinales/diagnóstico , Divertículo Ileal/patología , Adulto , Carcinoma de Células en Anillo de Sello/tratamiento farmacológico , Resultado Fatal , Femenino , Humanos , Neoplasias Intestinales/tratamiento farmacológico , PronósticoRESUMEN
BACKGROUND: Colorectal cancer (CRC) incidence increases sharply with age. In this study we assessed activity, toxicity and both the activity of daily living (ADL) and instrumental activity of daily living (IADL) of the De Gramont schedule in a series of advanced CRC patients aged > or = 70 years. PATIENTS AND METHODS: Sixty-two previously untreated advanced CRC patients entered the study. Median age was 75 (range 70-88). RESULTS: 447 courses were delivered. All of the 62 patients were evaluable for toxicity, 55 for response and ADL-IADL indexes. We recorded 2 complete and 9 partial responses, for an overall response rate of 20%. ADL and IADL indexes improved in 33%, remained stable in 49% and worsened in 18% of evaluable patients. Treatment was very well-tolerated with no serious hematological or non-hematological toxicities. CONCLUSIONS: The De Gramont schedule was very well tolerated in advanced CRC elderly patients, although our work could not confirm the original reported activity. ADL and IADL indexes improved or remained stable in 82% of evaluable patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Actividades Cotidianas , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/mortalidad , Estudios de Factibilidad , Femenino , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Leucovorina/efectos adversos , Masculino , Análisis de SupervivenciaRESUMEN
The purpose of this study was to survey the membership of the American Pain Society and the American Academy of Pain Medicine to determine their beliefs about ethical dilemmas in pain management practice. Respondents rated ethical dilemmas for their importance as well as their own competence in dealing with these ethical issues. The survey also included an open-ended question that asked respondents to describe clinical situations in which they had encountered ethical dilemmas. A total of 1,105 surveys were analyzed, with physicians (N = 612), nurses (N = 189), and psychologists (N = 166) representing the professions with the greatest response. Management of pain at the end of life, general undertreatment of pain, and undertreatment of pain in the elderly were the most frequently encountered dilemmas. Qualitative data were analyzed to identify ethical issues in the case examples provided by the respondents. Major themes included inappropriate pain management, barriers to care, interactions and conflicts with others, regulatory/legal issues, euthanasia, assisted suicide, and research issues. We conclude that ethical dilemmas are common in pain management practice and that resolution of these dilemmas requires commitment by individual professionals as well as health systems.
RESUMEN
BACKGROUND: The frequency of advanced non-small cell lung cancer (NSCLC) increases with age and more effective and less toxic chemotherapy schedules are needed in elderly patients. Cisplatin-based regimens are considered the best treatment for advanced NSCLC, although they produce only a modest advantage in overall survival with considerable toxicity. METHODS: In the present study the activity and toxicity of a weekly gemcitabine and cisplatin schedule was evaluated in a small group of advanced NSCLC patients aged 68 years or more. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on days 1, 8, 15 followed by 1 week of rest. RESULTS: Fifteen previously untreated patients entered the study; their median age was 72 years (range 68-76). One hundred and sixteen weekly administrations were delivered. The median dose-intensity was 614.5 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All the 15 patients were evaluable for response and toxicity. The overall response rate was 40% [95% CI = 16-68%]. The main toxicity was WHO grade III-IV thrombocytopenia that was recorded in 6 patients (40%). Other major toxicities were very low and no treatment-related deaths were reported. CONCLUSIONS: This schedule appears to be active, to have a favourable toxicity profile and can be considered in advanced NSCLC elderly patients. Of interest, the patients enrolled received high dose intensities of both drugs.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/administración & dosificación , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Desoxicitidina/administración & dosificación , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Proyectos Piloto , Tasa de Supervivencia , GemcitabinaRESUMEN
Managed care "backlash" rhetoric to the contrary, roadblocks to effective pain treatment occur both intrinsic and extrinsic to the healthcare system. Pain medicine, an emerging, formally recognized specialty, and the special population of patients which it serves, experience additional discreet barriers. Chief among these is a lack of clear identity and recognition of the specialty and the disenfranchisement of many of the patients it serves in the American healthcare system. Special problems within various healthcare financing environments is discussed.
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Accesibilidad a los Servicios de Salud , Manejo del Dolor , Dolor/prevención & control , Gobierno , Sector de Atención de Salud , Humanos , Programas Controlados de Atención en Salud/economía , Cuidados Paliativos , Rol del Médico , Atención Primaria de Salud , Estados Unidos , Indemnización para TrabajadoresRESUMEN
BACKGROUND: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule. PATIENTS AND METHODS: Thirty-six untreated patients with stage IIIB IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on day 1,8, and 15, followed by one week of rest. RESULTS: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%-57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4-23) and the median survival time 11.8 months (range 1-24). World Health Organization (WHO) grade 3-4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity. CONCLUSIONS: This regimen appears to be active and to have a favourable toxicity profile.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/administración & dosificación , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , GemcitabinaRESUMEN
In this study we evaluated the role of systemic chemotherapy in 23 previously untreated patients with brain metastases from both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). In NSCLC group, 2 patients out of 14 had a brain response after treatment (1 complete and 1 partial response). In the group of 9 patients with SCLC, we observed 5 brain responses (3 complete and 2 partial responses). Brain responses were in accordance with extracranial responses although this appeared more clearly in SCLC than in NSCLC patients.
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Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/uso terapéutico , Adulto , Anciano , Antineoplásicos Fitogénicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Células Pequeñas/secundario , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Paclitaxel/efectos adversos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
UNLABELLED: Unresectable primary hepatocellular carcinoma (HC) and liver metastases (LM) of abdominal tumors (AT) in progression after systemic chemotherapy (CT) have a poor prognosis and few therapeutic options. From 12/91 to 10/93 we treated 20 patients (PTS) 11 men and 9 women, with HC (10) and AT (10) with the following PCE: percutaneous placement of intraarterial hepatic catheter, superselective embolization with lipiodol (5 cc), infusion, mixed with lipiodol, of epirubicine 40 mg/m2, 5-fluorouracil 700 mg/m2, mitomycin-C 10 mg/m2 in 30'. After infusion, the arterial tree was embolized with Ivalon until an almost complete slowing of arterial blood-flow, every 5-6 weeks (W). After a median follow-up of 28 W a total of 35 courses had been administered to 20 PTS. Median (M) age was 69 years. M PS was 2. Okuda stage in HC PTS: 1 stage I, 9 stage II. in 10 HC PTS, positive for hepatitis B virus, CT and b-IFN had failed, while 10 AT PTS (5 colorectal, 2 gastric, 1 uterine, 1 larynx, 1 choledochus) had progressed, after, at least, 2 CT regimens, and had only LM. Median time from the diagnosis of LM in AT PTS was 32 W (12-68). TOXICITY: liver enzyme elevation and LDH elevation were 3 times baseline values, 4 PTS had fever for 6 days, 3 PTS had ileus for 3 days. No myelosuppression was observed. M alpha-fetoprotein value decreased from 468 ng/ml, to 56 ng/ml after PCE.(ABSTRACT TRUNCATED AT 250 WORDS)
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Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
Studies in this laboratory have shown that long term simian virus 40 (SV40)-specific cytolytic T lymphocyte (CTL) cultures established from the spleens of high responder C57BL/6 (B6; H-2b) mice exhibit a preference for the selection of H-2Db-restricted CTL clones. In this study, we have investigated the basis for this selection. Limiting dilution cultures were established using responder cells from the popliteal lymph nodes and the spleens of B6 mice immunized subcutaneously in the hind footpads or via the intraperitoneal route, respectively, with syngeneic SV40-transformed cells expressing a full length (1 to 708 amino acid residues) SV40 large T antigen. The relative frequency of CTL precursors (CTLp) able to expand in vitro in the presence of SV40-transformed stimulator cells and interleukin 2 and exhibit lytic activity against H-2b cells expressing full length T antigen ranged from 1/1900 to 1/15,000 in the popliteal lymph node and from 1/8000 to 1/55,000 in the spleen. In these two experimental systems, CTLp restricted to H-2Kb were apparently present at higher frequency than H-2Db-restricted CTLp. Furthermore, CTLp recognizing determinants within the amino-terminal or carboxy-terminal halves of T antigen were generated in approximately equal numbers. The relative affinity of SV40-specific CTL, assessed by inhibition with anti-Lyt 2 monoclonal antibody, indicated that CTL restricted to H-2Db interacted with their target with greater affinity than CTL restricted to H-2Kb. These data suggest that the predominance of isolation of H-2Db-restricted CTL clones from long term in vitro cultures may be a function of the relative affinity of this population as a whole, rather than due to the immunodominance of this subpopulation during the in vivo response to SV40 T antigen.
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Antígenos Transformadores de Poliomavirus/inmunología , Células Madre Hematopoyéticas/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Línea Celular , Epítopos , Antígenos H-2/inmunología , Antígeno de Histocompatibilidad H-2D , Isoanticuerpos/inmunología , Ganglios Linfáticos/inmunología , Ratones , Ratones Endogámicos C57BL , Bazo/inmunologíaRESUMEN
The kinetics of expression of the herpes simplex virus type 1-encoded major glycoprotein species gB, gC, gD, and gE on the surfaces of cells of murine, simian, and human origins were studied. Viable cells were stained with monoclonal antibodies specific for each species, and the levels expressed were determined by fluorescence flow cytometry. Differences were observed in both the kinetics and the levels of expression of individual glycoprotein species, depending upon the origin of the host cells. Glycoprotein gC was expressed early and at high levels in cells of murine and human origins, but late and at relatively low levels in simian cells. In contrast, gE was expressed at high levels in simian cells, but was not detectable until late in the infectious cycle in murine and human cells. The kinetics and levels of expression of gB were similar for all cells investigated, whereas gD, with high levels of expression in all cells late in infection, appeared on the surfaces of murine cells very early postinfection. This approach has allowed a simple quantitative method for comparing levels of glycoprotein expression.