RESUMEN

BACKGROUND: The observed occurrence of port site recurrence in laparoscopic surgery for malignant disease has stimulated interest in the dissemination of tumor cells during surgery. Study of electrocautery smoke has revealed the presence of large particles and viable viruses. The purpose of this study was to determine if viable malignant cells are present in suspension within the electrocautery plume. METHODS: Pellets of B16-F0 mouse melanoma cells were cauterized and the plume collected into culture medium. In part 1 of this study, the trypan blue assay was used to assess cell viability immediately after collection and 7 days later. A cautery current of 30 W was applied for 5 minutes. In part 2, the tetrazolium (MTT) viability assay was used to assess cell viability after cauterization of tumor pellets at 10, 20, and 30 W for 5 seconds. RESULTS: Although intact melanoma cells were identified with the trypan blue assay immediately after plume collection, no viable cells were seen at 7 days using this assay. In part 2, viable melanoma cells were present in the culture wells at 7 days. Lower fulguration currents appeared to yield higher cell counts: 2,250 cells/well at 10 W, 2,100 cells/well at 20 W, and 1,800 cells/well at 30 W. CONCLUSIONS: Results of this study confirm that application of electrocautery to a pellet of melanoma cells releases these cells into the plume. These cells are viable and may be grown in culture. This release of malignant cells may explain the appearance of port metastases at sites that are remote from the surgical dissection or that were never in direct contact with the tumor.

Asunto(s)

Electrocoagulación/efectos adversos , Melanoma Experimental/patología , Melanoma Experimental/cirugía , Siembra Neoplásica , Neoplasias Cutáneas/cirugía , Animales , Supervivencia Celular , Ratones , Complicaciones Posoperatorias , Neoplasias Cutáneas/patología , Células Tumorales Cultivadas

RESUMEN

We have evaluated the effect of antisense IGF receptor transcripts on the proliferation and tumorigenicity in an SV40-induced, immunocompetent hamster mesothelioma model (H9A). Expression of IGF-1 and IGF-1 receptor (IGF-1 R) genes was identified from H9A RNA using RT-PCR and Northern blot analysis. H9A cells were electroporated with inducible expression vectors (under the transcriptional control of heat shock promotor HSP70) containing a cDNA fragment corresponding to bp 1-309 of IGF-1 R in the sense or antisense orientation to generate the respective clones A3 sense or B9 antisense. At 39 degrees C, the B9 antisense transfectants demonstrated significantly less proliferation than A3 sense transfectants (p2 < 0.02). At 34 degrees C, cell growth of A3 sense and B9 antisense transfected cells was not significantly different. The A3 sense clones resulted in greater numbers of tumours in vivo compared to the B9 antisense clone (p2 = 0.0001). The inhibitory effect of IGF-1R antisense transcripts on hamster mesothelioma demonstrated in this study by decreased growth and tumorigenicity in vitro and in vivo may have implications for the therapy of human mesothelioma.

Asunto(s)

Mesotelioma/patología , Mesotelioma/virología , Oligonucleótidos Antisentido/farmacología , Neoplasias Pleurales/patología , Neoplasias Pleurales/virología , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/fisiología , Animales , Asbestosis/complicaciones , Transformación Celular Neoplásica/efectos de los fármacos , Cricetinae , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Mesotelioma/etiología , Plásmidos , Neoplasias Pleurales/etiología , Virus 40 de los Simios/aislamiento & purificación , Células Tumorales Cultivadas

RESUMEN

We found that simian virus 40 (SV40) induces mesotheliomas in hamsters and that 60% of human mesotheliomas contain and express SV40 sequences, results now confirmed by others [ref. 3-5, and presentations by D. Griffiths & R. Weiss, F. Galateau-SallE, and H.I.P. at "Simian virus 40: A possible human polyoma virus," NIH workshop, 27-28 January 1997, Bethesda, MD (transcript available through SAG Corp., Washington, DC 20008)]. Mesothelioma, an aggressive malignancy resistant to therapy, originates from the serosal lining of the pleural, pericardial and peritoneal cavities. The incidence of mesothelioma continues to increase worldwide because of exposure to crocidolite asbestos. However, at least 20% of mesotheliomas in the United States are not associated with asbestos exposure, and only a minority of people exposed to high concentrations of asbestos develop mesothelioma. Thus, other carcinogens may induce mesothelioma in individuals not exposed to asbestos, and/or may render particular individuals more susceptible to the carcinogenic effect of asbestos. We investigated whether the expression of the SV40 large T-antigen (Tag) interferes with the normal expression of the tumor suppressor gene p53 in human mesotheliomas. We found that SV40 Tag retains its ability to bind and to inactivate p53, a cellular protein that when normally expressed plays an important role in suppressing tumor growth and in inducing sensitivity to therapy. Our findings do not establish a cause-and-effect relation, but indicate that the possibility that SV40 contributes to the development of human mesotheliomas should be carefully investigated.

Asunto(s)

Antígenos Transformadores de Poliomavirus/metabolismo , Mesotelioma/metabolismo , Neoplasias Pleurales/metabolismo , Virus 40 de los Simios/inmunología , Proteína p53 Supresora de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Genes p53 , Humanos , Inmunohistoquímica , Mesotelioma/genética , Mesotelioma/patología , Mutación , Neoplasias Pleurales/patología , Unión Proteica , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética

RESUMEN

We investigated the structure and the expression of various oncogenes in three of the most common human bone tumors-osteosarcoma (36 samples from 34 patients), giant cell tumor (10 patients), and chondrosarcoma (18 patients)-in an attempt to identify the genetic alterations associated with these malignancies. Alterations of RB and p53 were detected only in osteosarcomas. Alterations of c-myc, N-myc, and c-fos were detected in osteosarcomas and giant cell tumors. Ras alterations (H-ras, Ki-ras, N-ras) were rare. Chondrosarcomas did not contain any detectable genetic alterations. Our results suggest that alterations of c-myc, N-myc, and c-fos oncogenes occur in osteosarcomas, in addition to those previously described for the tumor suppressor genes RB and p53. Moreover, statistical analyses indicate that c-fos alterations occur more frequently in osteosarcoma patients with recurrent or metastatic disease.

Asunto(s)

Neoplasias Óseas/genética , Oncogenes , Adolescente , Adulto , Anciano , Southern Blotting , Neoplasias Óseas/patología , Niño , Condrosarcoma/genética , Femenino , Genes Supresores de Tumor , Genes fos , Genes myc , Genes ras , Tumores de Células Gigantes/genética , Humanos , Masculino , Persona de Mediana Edad , Osteosarcoma/genética , Reacción en Cadena de la Polimerasa , Proteína p53 Supresora de Tumor/genética

RESUMEN

We evaluated the effect of antisense insulin-like growth factor (IGF) receptor transcripts on the proliferation and tumorigenicity in an SV40-induced, immunocompetent hamster mesothelioma model (H9A). Expression of IGF-1 and IGF-1 receptor (IGF-1R) genes was identified from H9A RNA using reverse transcription-PCR and Northern analysis. H9A cells were electroporated with inducible expression vectors (under the transcriptional control of heat shock promoter HSP70) containing a cDNA fragment corresponding to base pairs 1-309 of IGF-1R in the sense or antisense orientation to generate the respective clones A3 sense or B9 antisense. The expression vector in genomic DNA was detected with PCR analysis as a 173-bp fragment on ethidium bromide gels. The effects of the expression vectors were then evaluated in vitro under active (at 39 degrees C) or inactive (at 34 degrees C) conditions. At 39 degrees C, the B9 antisense transfectants demonstrated significantly less proliferation than A3 sense transfectants (P2 < 0.02). At 34 degrees C, cell growth of A3 sense- and B9 antisense-transfected cells was not significantly different. In vivo tumorigenicity was evaluated in hamsters inoculated with 10(5) A3 sense- or B9 antisense-transfected cells. The A3 sense clones resulted in greater numbers of tumors in vivo compared to the B9 antisense clone (P2 = 0.0001). When genomic DNA from tumors that developed in A3 sense and B9 antisense animals was analyzed for the expression vectors, a 173-bp fragment amplified from the expression vector was identified in the sense tumors but not in antisense B9 or wild-type H9A tumors, indicating a loss of the vector from the antisense clones that proliferated in vivo. The inhibitory effect of IGF-1R antisense transcripts on hamster mesothelioma demonstrated in this study by decreased growth and tumorigenicity in vitro and in vivo may have implications for the therapy of human mesothelioma.

Asunto(s)

Mesotelioma/prevención & control , Mesotelioma/ultraestructura , ARN sin Sentido/metabolismo , Receptor IGF Tipo 1/fisiología , Animales , Secuencia de Bases , División Celular/fisiología , Cricetinae , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Factor I del Crecimiento Similar a la Insulina/genética , Mesotelioma/metabolismo , Datos de Secuencia Molecular , Plásmidos/genética , Reacción en Cadena de la Polimerasa , ARN sin Sentido/genética , Ratas , Receptor IGF Tipo 1/genética , Transcripción Genética , Transfección , Células Tumorales Cultivadas

RESUMEN

BACKGROUND: A phase I trial was initiated to define the feasibility and safety of single-lung isolation perfusion with tumor necrosis factor-alpha, interferon-gamma, and moderate hyperthermia for patients with unresectable pulmonary metastases. METHODS: Twenty patients with lung metastases (Ewing's, 2; sarcoma, 8; melanoma, 6; other, 4) were considered for single-lung isolation perfusion with 0.3 to 6.0 mg of tumor necrosis factor-alpha and 0.2 mg interferon-gamma delivered through an oxygenated pump circuit. Sixteen perfusions were performed in 15 patients (bilateral in 1). Metastases were completely resected (no single-lung isolation perfusion) in 3 patients, 1 patient had extrapulmonary disease, and one single-lung isolation perfusion was aborted for mechanical reasons. RESULTS: There were no significant changes in systemic arterial blood pressure or cardiac output during perfusion. Systolic pulmonary artery pressure increased with isolation, but returned to pre-single-lung isolation perfusion levels after clamp release. The maximum systemic tumor necrosis factor-alpha level was 8 ng/mL, whereas pump-circuit levels ranged from 200 to 10,976 ng/mL. There were no deaths, and the mean hospitalization period was 9 days (range, 5 to 34 days). A short-term (6 to 9 month) unilateral decrease in perfused nodules was noted in 3 patients (melanoma in 1, adenoid cystic carcinoma in 1, renal cell carcinoma in 1). CONCLUSIONS: Future studies using a combination of biologic modifiers, chemotherapy, and hyperthermia should be pursued to define active cytotoxic agents that will preserve underlying pulmonary function.

Asunto(s)

Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Factor de Necrosis Tumoral alfa/uso terapéutico , Adulto , Presión Sanguínea , Carcinoma Adenoide Quístico/secundario , Carcinoma Adenoide Quístico/terapia , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/terapia , Gasto Cardíaco , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Hipertermia Inducida , Interferón gamma/uso terapéutico , Neoplasias Pulmonares/cirugía , Masculino , Melanoma/secundario , Melanoma/cirugía , Melanoma/terapia , Persona de Mediana Edad , Oxigenadores , Arteria Pulmonar , Inducción de Remisión , Seguridad , Sarcoma/secundario , Sarcoma/cirugía , Sarcoma/terapia , Sarcoma de Ewing/secundario , Sarcoma de Ewing/cirugía , Sarcoma de Ewing/terapia , Factor de Necrosis Tumoral alfa/administración & dosificación , Factor de Necrosis Tumoral alfa/análisis

RESUMEN

Pleural mesothelioma is an asbestos-related malignancy characterized by progressive local growth, late metastases, and median survivals between 8 and 18 months. It is only recently that the in vitro and in vivo characteristics of the malignancy has been investigated. These investigations have been aided by the development of cell lines from patients with the disease, as well as lines developed from asbestos-exposed animals. Nude mouse models constructed with subcutaneous, intraabdominal, or intrathoracic innoculation of cultured cell lines or fresh tumor have been used for evaluating response to innovative therapies. Karyotyping has been performed on a number of cell lines and multiple abnormalities involving many chromosomes have been identified. Aneuploidy is commonly seen, along with reported non-random patterns of chromosomal aberrations. The role of tumor suppressor genes, including p53 is controversial. Multiple growth factors including PDGF are being investigated for a possible paracrine/autocrine loop, and PDGF receptors seem to be differentially expressed in mesothelioma cells compared to normal mesothelial cells. The role of cytokines in the pathophysiology of the disease, secreted either by the tumor cells themselves or by monocyte/macrophages in the local tumor environment, remains to be defined.

Asunto(s)

Mesotelioma/patología , Neoplasias Pleurales/patología , Animales , Amianto/efectos adversos , Aberraciones Cromosómicas , Medios de Cultivo , Citocinas/biosíntesis , Citocinas/genética , ADN de Neoplasias/genética , Amplificación de Genes , Genes p53 , Sustancias de Crecimiento/genética , Humanos , Mesotelioma/etiología , Mesotelioma/genética , Ratones , Ratones Desnudos , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Trasplante de Neoplasias , Oncogenes , Neoplasias Pleurales/etiología , Neoplasias Pleurales/genética , Trasplante Heterólogo , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/trasplante

RESUMEN

Malignant pleural mesothelioma (MPM) is an asbestos-related disease which, although rare, is having a major social impact, and is, for the majority of cases, an incurable illness. There has been a surge of information regarding data on mesothelial transformation, mesothelioma molecular genetics and somatic gene therapy for this disease. This report summarizes the most recent investigations attempting to characterize the behaviour, on a cellular and molecular level, of MPM, with an emphasis on data from investigations performed at the National Cancer Institute with our collaborators.

Asunto(s)

Mesotelioma , Neoplasias Pleurales , Asbestosis/complicaciones , Secuencia de Bases , Aberraciones Cromosómicas/etiología , Trastornos de los Cromosomas , Citocinas/metabolismo , Daño del ADN , Genes Supresores de Tumor , Terapia Genética , Humanos , Mesotelioma/etiología , Mesotelioma/genética , Mesotelioma/metabolismo , Mesotelioma/terapia , Mesotelioma/virología , Datos de Secuencia Molecular , Neoplasias Pleurales/etiología , Neoplasias Pleurales/genética , Neoplasias Pleurales/metabolismo , Neoplasias Pleurales/terapia , Neoplasias Pleurales/virología , Especies Reactivas de Oxígeno/metabolismo , Virus 40 de los Simios/genética

RESUMEN

This report characterizes nine new cell lines derived from patients with malignant pleural mesothelioma. The lines were initiated between July 1990 and July 1992 from solid tumors (5 lines) or effusions (4 lines) and had proliferated for a period of at least 2 months without senescence. They were characterized by cell size, doubling time, immunohistochemical analyses, electron microscopy, and chromosomal karyotyping. Growth factor/cytokine elaboration was determined using enzyme-linked immunoassays. The established lines were similar in morphology to their parent tumor (ie, epithelial or sarcomatoid). Cell sizes ranged from 59 to 81 microns, and the doubling times varied from 31 to 65 hours. The lines stained with cytokeratin and showed expected negative staining for adenomarkers including B72.3 and carcinoembryonic antigen. All cell lines exhibited aneuploidy, with modal chromosome numbers between 40 and 81 and had multiple chromosomal aberrations. Significant production of granulocyte-monocyte colony-stimulating factor, leukemia inhibitory factor, platelet-derived growth factor, and interleukin-6 was seen. These new cell lines derived from human mesotheliomas can now be used to aid in the design of innovative treatment strategies.

Asunto(s)

Mesotelioma , Neoplasias Pleurales , Células Tumorales Cultivadas , Adulto , Anciano , División Celular , Medios de Cultivo , Citocinas/biosíntesis , Femenino , Humanos , Inmunohistoquímica , Cariotipificación , Masculino , Mesotelioma/química , Mesotelioma/genética , Mesotelioma/metabolismo , Mesotelioma/patología , Mesotelioma/ultraestructura , Persona de Mediana Edad , Neoplasias Pleurales/química , Neoplasias Pleurales/genética , Neoplasias Pleurales/metabolismo , Neoplasias Pleurales/patología , Neoplasias Pleurales/ultraestructura , Células Tumorales Cultivadas/química , Células Tumorales Cultivadas/metabolismo , Células Tumorales Cultivadas/patología , Células Tumorales Cultivadas/ultraestructura

RESUMEN

We have found 16 of 28 small cell lung cancers, 17 of 31 non-small cell lung cancers, 2 of 3 carcinoids, and 12 of 14 mesotheliomas that had chromosome 22 cytogenetic abnormalities. To determine whether the neurofibromatosis type 2 (NF2) gene located on chromosome 22 participates in the oncogenesis of these malignancies, we studied DNAs from lung cancer cell lines and mesotheliomas using Southern blot analysis and the single-strand conformation polymorphism (SSCP) technique for mutations covering 8 of the 16 known NF2 exons. We detected 7 mutations in 17 mesotheliomas (41%) within the coding region of NF2 but none in 75 lung cancer cell lines (38 small cell lung cancers, 34 non-small cell lung cancers, and 3 carcinoids). These mutations were found to be somatic when normal tissue was available for testing. Four mesothelioma cell lines had relatively large deletions (approximately 10-50 kilobases) in the NF2 gene detectable by Southern blot analysis. Two mesothelioma cell lines had nonsense mutations at codons 57 and 341, respectively. Another mesothelioma obtained as a specimen directly from a patient, had a 10-base pair microdeletion from nucleotide 1004 to nucleotide 1013 causing a frameshift mutation. These results suggest that the NF2 gene participates in the oncogenesis in a subset of mesotheliomas but not in lung cancers.

Asunto(s)

Genes de la Neurofibromatosis 2 , Neoplasias Pulmonares/genética , Mesotelioma/genética , Mutación , Secuencia de Bases , Cromosomas Humanos Par 22 , Proteínas de Unión al ADN/genética , Eliminación de Gen , Genes Supresores de Tumor , Humanos , Datos de Secuencia Molecular , Factores de Transcripción/genética , Células Tumorales Cultivadas , Proteínas WT1

RESUMEN

A complex interplay of peptides known as the cytokines may have a tremendous influence over a number of inflammatory related conditions. Tumor necrosis factor occupies an early and central role in the initiation of cascades that ultimately influences a number of cell types involved in tissue inflammation, tissue rejection, cancer, and injuries from ischemia reperfusion. Only now are the cascades being defined and therapies being designed to interrupt the toxic effects of these cytokines and to treat malignancy.

Asunto(s)

Citocinas/fisiología , Macrófagos/fisiología , Factor de Necrosis Tumoral alfa/fisiología , Animales , Anorexia/etiología , Ensayos Clínicos como Asunto , Factores Estimulantes de Colonias/fisiología , Cricetinae , Citocinas/antagonistas & inhibidores , Citocinas/uso terapéutico , Rechazo de Injerto/etiología , Cardiopatías/etiología , Humanos , Inmunoterapia , Técnicas In Vitro , Interferones/fisiología , Interleucinas/fisiología , Leucemia/terapia , Ratones , Neoplasias/fisiopatología , Neoplasias/terapia , Síndrome de Dificultad Respiratoria/etiología , Choque Séptico/etiología , Factor de Necrosis Tumoral alfa/uso terapéutico

RESUMEN

Induction of mesothelioma in the rat is an important animal model for assessing the carcinogenic potential of fibers and for understanding the molecular basis underlying the development of these tumors. Mesotheliomas and nephroblastoma (Wilms' tumor) have many developmental, biochemical, and histological similarities; however, the expression of the Wilms' tumor suppressor gene, WT-1, has not been well characterized in the rat, and its expression pattern in rat or human mesothelioma has not been described. We report that WT-1 transcripts (3.2 kilobases) could be detected by Northern analysis in adult rat testis, spleen, kidney, lung, heart, and glomerular mesangial cells. Normal adult mesothelial cells also expressed this gene. Rat mesothelioma cell lines expressed WT-1 transcripts of 3.2 kilobases and an additional 2.8-kilobase transcript, previously only reported to be expressed in the testis. Normal and transformed rat mesothelial cells expressed all four of the WT-1 splice variants, except testis, which only expressed WT-1 splice variants containing exon 5. Seven of seven human mesothelioma cell lines examined also expressed WT-1 transcripts, suggesting that expression of this gene may be useful in the diagnosis of these tumors.

Asunto(s)

Genes del Tumor de Wilms , Mesotelioma/genética , Anciano , Empalme Alternativo , Animales , Amianto/efectos adversos , Secuencia de Bases , Transformación Celular Neoplásica/genética , Exones , Expresión Génica , Humanos , Masculino , Mesotelioma/inducido químicamente , Persona de Mediana Edad , Datos de Secuencia Molecular , Especificidad de Órganos , Ratas , Testículo/fisiología

RESUMEN

Mesotheliomas are pleural, pericardial, or peritoneal neoplasms frequently associated with asbestos exposure, and it is estimated that over the next twenty years up to 80,000 new cases are expected in the USA alone. We found simian virus 40-like DNA sequences in 29 of 48 mesotheliomas studied (60%) and demonstrated simian virus large-T antigen expression in 13 of 16 specimens. The matching lung samples did not contain simian virus 40-like sequences; however, they contained asbestos. These findings are to our knowledge the first demonstration of a physical link between DNA virus-like sequences and human mesothelioma. We suggest that a simian virus 40-like virus may act independently or as a co-carcinogen with asbestos. Moreover, the selective large T antigen expression by mesothelioma and not by the surrounding pulmonary parenchyma may have both diagnostic and therapeutic implications.

Asunto(s)

ADN Viral/análisis , Mesotelioma/microbiología , Neoplasias Pleurales/microbiología , Virus 40 de los Simios/genética , Adulto , Anciano , Antígenos Transformadores de Poliomavirus/análisis , Amianto/efectos adversos , Secuencia de Bases , ADN Viral/química , Femenino , Humanos , Masculino , Mesotelioma/diagnóstico , Mesotelioma/etiología , Persona de Mediana Edad , Datos de Secuencia Molecular , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/etiología , Reacción en Cadena de la Polimerasa , Virus 40 de los Simios/inmunología , Proteínas Virales/análisis

RESUMEN

A variety of cell lines have been prepared by fusion of the murine WEH1 3B cell line with peripheral blood leukocytes from a patient with chronic granulocytic leukemia. Fusion products were selected for their ability to produce a leukemia-associated antigen (CAMAL) previously described. One such line which originally produced CAMAL subsequently lost this ability and was used as a negative control. A number of antibodies were conjugated to hematoporphyrin (HP) and tested for their ability to bind to cell lines as detected by either fluorescence or by their ability to kill cells after light activation. The antibodies used were: rabbit anti-Hu (a conventional rabbit antiserum raised to membrane preparations from normal human peripheral blood leukocytes which served as a positive control); CAMAL-1 (a monoclonal gamma 1 antibody with specificity for the CAMAL antigen); and L1210 (an irrelevant monoclonal gamma 1 antibody). HP was conjugated to the antibodies by a carbodiimide procedure. When labeled cells were examined by fluorescence microscopy, it was apparent that both the rabbit antibody and CAMAL-1:HP showed positive labeling. The ability of the antibody:HP conjugates to kill labeled cells following light activation was tested. It was shown that rabbit anti-Hu:HP and CAMAL-1:HP conjugates were capable of killing significant numbers of cells when HP concentrations were as low as 1.2 ng/10(6) cells, whereas similarly treated cells exposed to either L1210:HP or HP alone did not exhibit significant killing until concentrations reached 240 and 120 ng/10(6) cells, respectively. Further experiments in which other cell lines were tested, all at HP concentrations of 12 ng/10(6) cells, demonstrated that those lines producing CAMAL were killed, whereas negative lines were not.

Asunto(s)

Anticuerpos Monoclonales/administración & dosificación , Hematoporfirinas/administración & dosificación , Sueros Inmunes/administración & dosificación , Neoplasias/terapia , Fotoquimioterapia , Animales , Antígenos de Neoplasias/análisis , Línea Celular , Hematoporfirinas/uso terapéutico , Humanos , Leucemia/inmunología , Ratones , Neoplasias/inmunología , Conejos

Asunto(s)

Hematoporfirinas/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Eritrocitos/inmunología , Derivado de la Hematoporfirina , Hemólisis , Humanos

RESUMEN

The term "photoimmunotherapy" describes an anti-cancer treatment that combines the phototoxic effects of chemical such as hematoporphyrin and the target-seeking ability of antibodies. Hematoporphyrin was chemically coupled to monoclonal antibodies directed to the DBA/2J myosarcoma M-1. Administration of anti-M-1-hematoporphyrin conjugates i.v. to M-1 tumor-bearing animals followed by exposure to incandescent light resulted in suppression of M-1 growth. The time interval between injection and light exposure was an important parameter in terms of tumor suppression. Tumor-bearing animals maintained in the dark for 96 to 196 hr after hematoporphyrin-antibody injection followed by 4-hr light exposure demonstrated significantly lower tumor incidence and longer latency periods, in comparison to conjugate-treated animals instantly exposed to light. The growth inhibiting properties of the conjugate appeared to be M-1-specific; it had no effect on the growth of a C57BL/6J lymphoma EL4. In addition, conjugates made with a nonspecific monoclonal antibody did not have any specific anti-tumor effect on M-1 growth. Treatment with equivalent doses of hematoporphyrin or antibody had no significant inhibiting effect on tumor growth. Clearly, the homing ability of the specific monoclonal antibody-hematoporphyrin conjugate was essential for effective drug delivery and inhibition of tumor growth.

Asunto(s)

Anticuerpos Monoclonales/administración & dosificación , Hematoporfirinas/uso terapéutico , Inmunoterapia , Fototerapia , Animales , Epítopos , Femenino , Hibridomas/inmunología , Linfoma/terapia , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Rabdomiosarcoma/terapia

Asunto(s)

Antineoplásicos Fitogénicos , Sesquiterpenos/farmacología , Animales , Femenino , Leucemia L1210/tratamiento farmacológico , Ratones , Ratones Endogámicos DBA

RESUMEN

The anti-tumour effects of the sesquiterpene lactone, parthenin was studied both in vivo and in vitro. Parthenin showed marked cytotoxic activity to P815 mastocytoma, L1210 leukemia, and M-1 rhabdomyosarcoma cells in vitro. In vivo studies showed intraperitoneal drug administration could either cure mice or increase their survival time after intraperitoneal of subcutaneous injection with tumour cells.