RESUMEN
The relationship between sensitivity to anti-cancer agents and EGF receptor expression on squamous cell carcinoma (SCC) cells was investigated. The cytotoxicity of peplomycin (PEP) was correlated with the number of the EGF receptors expressed on the cancer cells, but no correlations were found between the cytotoxicity of adriamycin and cisplatin and EGF receptors. Addition of TNFalpha increased the number of EGF receptors in the SCC cell lines 1.5- to 2-fold. The cytotoxic effect of combined administration of PEP and TNFalpha was correlated with the number of EGF receptors, and produced a 2- to 5-fold increase in IC50 compared with administration of PEP alone. These observations suggest that EGF receptor expression is closely associated with the cytotoxic effect of PEP on SCC cells.
Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Carcinoma de Células Escamosas/tratamiento farmacológico , Receptores ErbB/metabolismo , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Gingivales/tratamiento farmacológico , Peplomicina/toxicidad , Células Tumorales Cultivadas/efectos de los fármacos , Neoplasias de la Vulva/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Carcinoma de Células Escamosas/metabolismo , Supervivencia Celular , Cisplatino/toxicidad , Doxorrubicina/toxicidad , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias Esofágicas/metabolismo , Femenino , Neoplasias Gingivales/metabolismo , Humanos , Análisis de Regresión , Células Tumorales Cultivadas/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Neoplasias de la Vulva/metabolismoRESUMEN
BACKGROUND: The timing and length of administration of angiogenesis inhibitor TNP-470 was altered to evaluate the effect on disease progression in a rat model of colorectal hepatic metastases. METHODS: Pair-fed BD-IX rats, injected intrasplenically with rat colon adenocarcinoma K12/TRb cells at day 0, were randomized to receive subcutaneous injections of either placebo or 15 mg/kg TNP-470 on alternate days: for 2 weeks beginning 24 hours after tumor inoculation ("Early"), for 4 weeks beginning 24 hours after tumor inoculation ("Prolonged"), or for 2 weeks beginning at day 15 after macroscopic tumor nodules were confirmed ("Delayed"). Response to treatment was evaluated by counting tumor nodules on the surface of the liver at laparotomy on day 14 and 28 after tumor inoculation. The animals were followed for survival and cause of death. RESULTS: Maximal suppression of hepatic metastases at day 28 required 4-week rather than 2-week TNP-470 administration. Prolonged TNP-470 administration resulted in significantly fewer hepatic metastases at day 28 compared to control (P < .05). Early and prolonged TNP-470 improved survival (Wilcoxon test, P < .05) compared with delayed TNP-470 and placebo. Delayed TNP-470 administration did not increase survival or significantly diminish the number of metastases at day 28 compared with placebo. CONCLUSIONS: These data suggest that prolonged adjuvant antiangiogenic therapy may suppress colorectal hepatic micrometastases.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/secundario , Neovascularización Patológica/prevención & control , Sesquiterpenos/uso terapéutico , Animales , Neoplasias Colorrectales/patología , Ciclohexanos , Masculino , O-(Cloroacetilcarbamoil) Fumagilol , Ratas , Sesquiterpenos/toxicidad , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
We studied the prognoses of unresectable liver tumors, including 31 colorectal cancers and 10 gastric cancers treated by intra-arterial infusion chemotherapy using an implantable reservoir. Adriamycin, epirubicin, or cisplatin were administered intermittently early on. Cisplatin and 5-FU combined therapy were given later. In nine with colorectal metastases and six with gastric metastases, metastatic lesions decreased, and in 4 patients with metastatic lesions could be resected. But in many patients, hepatic and other organ recurrences were observed. We need to try many other treatments.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bombas de Infusión Implantables , Neoplasias Hepáticas/tratamiento farmacológico , Adenocarcinoma/secundario , Anciano , Cisplatino/administración & dosificación , Neoplasias del Colon/patología , Doxorrubicina/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
We determined in vitro the antitumor activity of a conjugate prepared by binding a monoclonal antibody (B4G7), which recognizes the human epidermal growth factor (EGF) receptor, with peplomycin (PEP), which is an antitumor agent effective against squamous cell carcinoma. This B4G7-PEP conjugate was prepared by coupling of B4G7 and carboxymethylpeplomycin active ester. The conjugate killed A431 cells of squamous cell carcinoma which overexpress EGF receptors at lower concentrations than PEP alone. On the basis of its IC50, the conjugate was six times more potent than PEP alone. A simple mixture of B4G7 and PEP was as effective as PEP alone in cytotoxicity. The addition of ten times the amounts of B4G7 to this conjugate decreased its cytotoxicity. When other squamous cell carcinoma cell lines with different levels of EGF receptors (NA, Ca9-22, TE-1, TE-8) were treated with the conjugate, cells were killed dose-dependently and the cytotoxicity was dependent on the number of EGF receptors. When each squamous cell carcinoma cell line was treated with a control conjugate prepared by combining PEP with mouse IgG instead of B4G7, no cytotoxicity was observed. These results indicate that B4G7-PEP will be a useful weapon in multidisciplinary treatment which utilizes the EGF receptor, as these receptors are detected in a higher incidence in squamous cell carcinoma.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Bleomicina/uso terapéutico , Carcinoma de Células Escamosas/terapia , Receptores ErbB/metabolismo , Inmunotoxinas/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Carcinoma de Células Escamosas/metabolismo , Supervivencia Celular , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Peplomicina , Células Tumorales CultivadasRESUMEN
An extended lymphadenectomy including cervical node dissection is one of the most difficult operations, therefore its merits and demerits should be assessed in order to evaluate whether it has the significance of extended radical operation or not. Extended lymphadenectomies including cervical node dissection became to be the standard procedures of lymphadenectomy for cases with cancer of the thoracic esophagus from 1986, and were carried out in 42 cases. Survival rates, disease free survival rates, sites of recurrences and incidences of postoperative complications were compared with the of cases with conventional lymphadenectomy excluding cervical node dissection. Concerning over all survival rates, no significant differences were observed between extended and conventional groups. However only in cases of stage 0 I II, significant difference in survival rates were observed between two groups. Therefore based on our experience, the merit of extended lymphadenectomy was observed only in stage 0 I II cases which had no lymph node metastasis. Concerning the incidence of postoperative complications, no significant differences were observed between two groups, therefore the significance of proceeding extended lymphadenectomy was confirmed.