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1.
Journal of Korean Medical Science ; : 1160-1163, 2016.
Artigo em Inglês | WPRIM | ID: wpr-13343

RESUMO

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.


Assuntos
Idoso , Humanos , Masculino , Aminopterina/efeitos adversos , Antineoplásicos/efeitos adversos , Bortezomib/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Linfoma de Células T Periférico/diagnóstico por imagem , Recidiva Local de Neoplasia , Neutropenia/etiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
2.
Immune Network ; : 128-137, 2006.
Artigo em Inglês | WPRIM | ID: wpr-61957

RESUMO

BACKGROUND: Apoptosis is a physiologic phenomenon involved in development, elimination of damaged cells, and maintenance of cell homeostasis. Deregulation of apoptosis may cause diseases, such as cancers, immune diseases, and neurodegenerative disorders. The mouse myeloma cell P3-X63-Ag8.653 (v653) is an HGPRT deficient (HGPRT) mutant strain. High dependency on de novo transcription and translation of aminopterin induced apoptosis of this cell seems to be an ideal experimental system for searching apoptosis-induced genes. METHODS & RESULTS: For searching apoptosis-related genes we carried out GE-array (dot blot), Affymetrix GeneChip analysis, Northern analysis and differential display-PCR techniques. The chip data were analyzed with three different programs. 66 genes were selected through Affymetrix GeneChip analyses. All genes selected were classified into 8 groups according to their known functions. They were Genes of 1) Cell growth/maintenance/death/ enzyme, 2) Cell cycle, 3) Chaperone, 4) Cancer/disease-related genes, 5) Mitochondria, 6) Membrane protein/signal transduction, 7) Nuclear protein/nucleic acid binding/ transcription binding and 8) Translation factor. Among these groups number of genes were the largest in the genes of cell growth/maintenance/death/enzyme. Expression signals of most of all groups were peaked at 3 hour of apoptosis except genes of Nuclear protein/nucleic acid binding/ transcription factor which showed maximum signal at 1 hour. CONCLUSION: This study showed induction of wide range of proapoptotic factors which accelerate cell death at various stage of cell death. In addition apoptosis studied in this research can be classified as a type 2 which involves cytochrome c and caspase 9 especially in early stages of death. But It also has progressed to type 1 in late stage of the death process.


Assuntos
Animais , Camundongos , Aminopterina , Apoptose , Caspase 9 , Ciclo Celular , Morte Celular , Citocromos c , Homeostase , Hipoxantina Fosforribosiltransferase , Doenças do Sistema Imunitário , Membranas , Mitocôndrias , Doenças Neurodegenerativas , Fatores de Transcrição
3.
Rev. chil. ultrason ; 8(3): 74-80, 2005. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-425237

RESUMO

El metotrexato es un antimetabolito del ácido fólico que interfiere en la síntesis del ADN y es utilizado en patologías oncológicas, reumatológicas, dermatológicas y gineco-obstétricas. Su uso durante el primer trimestre de gestación puede provocar malformaciones fetales pesquisables en la evaluación ultrasónica prenatal; el conjunto de estas malformaciones congénitas asociadas al uso de metotrexato han recibido el nombre de síndrome aminopterina / metotrexato. Este síndrome se caracteriza por malformaciones evolutivas del Sistema Nervioso Central, anormalidades esqueléticas y a largo plazo, de manera inconstante, retraso mental. Presentamos dos casos clínicos ilustrativos de este síndrome, en conjunto con el Servicio de Obstetricia y Ginecología del Hospital San Juan de Dios del Servicio de Salud Metropolitano Occidente. En Chile la magnitud de este síndrome es desconocida y el aborto no es social ni legalmente aceptado, por lo que adquiere importancia conocer esta patología y sus consecuencias por parte del equipo de salud.


Assuntos
Adulto , Humanos , Feminino , Gravidez , Recém-Nascido , Anormalidades Induzidas por Medicamentos , Feto/anormalidades , Metotrexato/efeitos adversos , Ultrassonografia Pré-Natal , Aborto Criminoso , Ácido Fólico/efeitos adversos , Aminopterina/efeitos adversos , Chile
4.
Journal of the Korean Cancer Association ; : 655-664, 2000.
Artigo em Coreano | WPRIM | ID: wpr-10750

RESUMO

PURPOSE: When murine myeloma cells P3-X63-Ag8.653 (V653) of this model treated with amin opterin, an anticancer drug, they can't synthesize nucleic acid via de novo or salvage pathway and selectively eliminated due to apoptosis. This study was aimed to clone specific known and novel genes preferentially expressed in aminopteirn-treated tumor cell apoptosis. MATERIALS AND METHODS: This study was aimed to clone specific known and novel genes pre ferentially expressed in aminopteirn-treated tumor cell apoptosis by using subtraction-PCR technique. RESULTS: By using this technique 868 clones were obtained. Of these 427 clones were positive with insert DNA. By using cross-hybridization Southern blotting, final 101 clones were selected. All of these genes were sequenced and analyzed by using genebank DNA database. Total 101 clones of genes preferentially expressed in apoptotic tumor cells were classified into 10 groups, which included ribosomal proteins, nuclear proteins, mitdegrees Chondrial proteins, signal transductional proteins, retroviral proteins, cell surface receptor proteins, cell structural proteins, unclassified miscellaneous proteins, and novel genes. Especially, Unknown novel genes preferentially ex pressed in this apoptotic tumor cells included clone numbers S1-63, 1-1, 1-3, 1-16, 1-18, 1-20, 3-33, 3-41, 3-44, 3-48, 3-55, 3-60, 6-17, 6-25, 8-12, 50-7, 50-23, and 100-35. CONCLUSION: It seemed that known and unknown novel genes cloned in this study would con tribute to the future studies regarding apoptosis of tumor cells and cancer treatment therepy.


Assuntos
Aminopterina , Apoptose , Southern Blotting , Células Clonais , Clonagem de Organismos , Bases de Dados de Ácidos Nucleicos , DNA , Programas de Rastreamento , Proteínas de Membrana , Proteínas Nucleares , Proteínas Ribossômicas , Zidovudina
5.
Korean Journal of Immunology ; : 25-34, 1999.
Artigo em Coreano | WPRIM | ID: wpr-181229

RESUMO

Programmed cell death (PCD), or apoptosis, plays an important role in embryonic development, metamorphsis, hormone-dependent atrophy and tumor growth, as a physiological event regulating the cell number or eliminating damaged cells. Currently hybridoma cell production, resulting from the fusion of myeloma cells with antibody producing spleen cells, is widely used in various fields of life science. This technique requires a hypoxanthine guanine phosphoribosyl transferase (HGPRT) deficient mutant myeloma cell line as a fusion partner. When these rnutant cells are treated with aminopterin plus hypoxanthine-thymidine (HAT) after the cell fusion they are selectively and efficiently eliminated so that one could get only fused hybridoma cells. But there hasn't been any report regarding this selective elimination mechanism of HGPRT mutant myeloma cell. By using HGPRT myeloma V653 as a model system this study demonstrated that PCD was induced by aminopterin treatment of this V653 cell. And this PCD was further characterized by cotreatement of cycloheximide, actinomycin-D, and calcium ionophore A23187 together with aminopterin. The apoptotic endonuclease involved in this PCD process was also detected and characterized. When V653 cells were incubated for the various periods of time in the presence of 0.4 uM aminopterin, the viability was continued to decrease until 48 hours of aminopterin treatment and there was no viable cell affer 36 hours of incubation. DNA fragmentation was detectable 3 hours of incubation and peaked between 12 and 18 hours of aminopterin treatment. The induction of cell death and DNA fragmentation of V653 cells by aminopterin were inhibited by protein synthesis inhibitor, cycloheximide, and RNA synthesis inhibitor, actinomycin-D and maximal inhibitory effects on cell death were seen at concentrations of 2 ug/ml and 0.5 uM, respectively. Ca2+ ionophore A23187 promoted aminopterin-induced cell death of V653. When the cells were coincubated with A23187 in the presence of aminopterin, cell viability was remarkably decreased at concentrations of more than 2 uM and DNA fragmentation was increased at concentrations of more than 0.2 uM. A23187 also induced cell death when the cells were treated with A23187 alone. When endogenous endonuclease activities of nuclei isolated from intact healthy cells and aminopterin-treated cells were compared for four different conditions, there were notable increases in the Ca2+/Mg2+ -independent and the Mg2+ -dependent endonuclease activity after incubation with aminopterin for 12 hours. In northern blot analysis, induction of c-myc gene was observed in aminopterin-treated V653 cell reached peak at 2 hours and thern decreased drastically.


Assuntos
Animais , Feminino , Camundongos , Gravidez , Aminopterina , Apoptose , Atrofia , Disciplinas das Ciências Biológicas , Northern Blotting , Calcimicina , Cálcio , Contagem de Células , Morte Celular , Fusão Celular , Linhagem Celular , Sobrevivência Celular , Cicloeximida , Fragmentação do DNA , Desenvolvimento Embrionário , Genes myc , Guanina , Hibridomas , Hipoxantina , Hipoxantina Fosforribosiltransferase , RNA , Baço , Transferases
6.
Korean Journal of Immunology ; : 389-396, 1998.
Artigo em Coreano | WPRIM | ID: wpr-75545

RESUMO

Programrned cell death (PCD), or apoptosis, is a process by which cells die in response to specific physiological and toxicological signals. This genetically programmed form of cellular suicide is intirnately involved in many biological processes including growth, metamorphosis, embryogenesis, and oncogenesis. Cells undergoing PCD in normal and neoplasmic tissues display the following biochemical and morphological features: internucleosomal DNA fragmentation, reduced cell volume, condensed chromatin in nucleus, zeiosis and generation of apoptotic bodies containing intact organelles and plasma rnembrane. Hybridoma cell production, resulting from the fusion of myeloma cells with antibody producing spleen cells, is widely used in various fields of life science. This technique requires hypoxanthine guanine phosphoribosyl transferase (HGPRT) deficient mutant myeloma cell line as a fusion partner. When these mutants cell is treated with aminopterin plus hypoxanthine-thymidine (HAT) after the cell fusion they are selectively and efficiently eliminated remaining fused hybridoma celis. But there hasn't been any report regarding the selective elimination mechanism of this HGPRT mutant myeloma cell. By using HGPRT myeloma P3-X 63-Ag8.653 (V653) as a model system, this study demonstrated that PCD was induced by aminopterin treatment of this V653 cell line. And the sequential ultrastructural changes during this death process were observed by using electron microscope. When V653 cells were incubated with 0.4 uM aminopterin, DNA fragmentation was detectable after 3 hours and peaked between 12 and 18 hours of aminopterin treatment and the cell viability decreased in a time dependant manner. V653 cells incubated with amiopterin showed following ultrastructural changes during the death process. Dilatation of rough endoplasmic reticulum (RER) and detachment of ribosomes were the earliest ultrastructural changes and first seen after 30 minute incubation. Dilatation of perinuclear cisternae began to appear after 1 hour and deformation of nucleoplasm such as decreased electron density of perinuclear heterochromatin and increased electron density of euchromatin were seen after 3 hours. Increased electron density of cytoplasm, decreased cell volume, condensation of chromatin and apoptotic bodies were observed in many cells after 9 hours but vacuolation by severe dilatation of RER was seen in some cells. 24 hours after incubation with aminopterin, many cells showed typical form of apoptosis characterized by cell shrinkage, increased electron density of cytoplasm and apoptotic bodies. On the contrary, some cells showed different type of cell death characterized by increased cell volume, decreased electron density of cytoplasm, severely dilated RER and apoptotic bodies. In both types of cells, mitochondrial cristae and limiting membrane of mitochondria are comparatively well preserved. In other cells, nuclei did not show significant changes but there were deformations of mitochondria such as markedly increased electron density and formation of lamella bodies. The death process of V653 cell was not synchronized among cells. The results of this study proved that aminopterin-induced selective elimination of fusion partner V653 myeloma cell is due to PCD. The earliest ultrastructural changes observed in this process were dilatation of RER and detachment of ribosomes. And there were two distinct morphological types in the PCD.


Assuntos
Animais , Feminino , Camundongos , Gravidez , Aminopterina , Apoptose , Fenômenos Biológicos , Disciplinas das Ciências Biológicas , Carcinogênese , Morte Celular , Fusão Celular , Linhagem Celular , Tamanho Celular , Sobrevivência Celular , Cromatina , Citoplasma , Dilatação , Fragmentação do DNA , Desenvolvimento Embrionário , Retículo Endoplasmático Rugoso , Eucromatina , Guanina , Heterocromatina , Hibridomas , Hipoxantina , Hipoxantina Fosforribosiltransferase , Membranas , Mitocôndrias , Organelas , Plasma , Ribossomos , Baço , Suicídio , Transferases
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