RESUMEN
A woman in her 80s reported of generalised pruritus, which was treated with phototherapy and steroid administration. Two months after onset, lymph node biopsy revealed CD4+ angioimmunoblastic T-cell lymphoma with systemic superficial nodal involvement. Intractable prurigo was judged as T-cell lymphoma related. After effective chemotherapy (7 months later), skin nodules appeared multifocally, including on the lip, thumb and lower leg. The biopsied infiltrative lesion on the right lower leg microscopically revealed subcutaneous growth of atypical plasmablasts with nearly 100% Ki-67 labelling and Epstein-Barr virus (EBV)-encoded small nuclear RNA positivity. Plasmablastic lymphoma (CD45/CD19/CD38/CD138/MUM1+, CD20/CD79a/PAX5-) was suspected. Immunoglobulin light-chain restriction and nuclear expression of c-myc protein were undetectable, and the ulcers were spontaneously epithelialised by the cessation of steroid administration. After 10 months, non-progressive prurigos persisted on the extremities, but without regrowth of nodal T-cell lymphoma and cutaneous lymphoproliferative lesion. Reactive nature of the EBV-induced mucocutaneous plasmablastic growth (EBV-positive mucocutaneous ulcer, plasmablastic type) is discussed.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma de Células T , Trastornos Linfoproliferativos , Linfoma Plasmablástico , Lesiones Precancerosas , Linfocitos T CD4-Positivos , Femenino , Herpesvirus Humano 4 , Humanos , Linfoma de Células T/complicaciones , Trastornos Linfoproliferativos/patología , Linfoma Plasmablástico/complicaciones , Linfoma Plasmablástico/diagnóstico , Prurito , Esteroides , Úlcera/complicacionesRESUMEN
CONTEXT.: Recent advances in comprehensive genomic profiling by next-generation sequencing have uncovered the genomic alterations at the molecular level for many types of tumors; as such, numerous small specific molecules that target these alterations have been developed and widely used in the management of these cancers. OBJECTIVE.: To provide a concise molecular genomic update in solid, bone and soft tissue tumors, hematopoietic as well as lymphoid malignancies; discuss its clinical applications; and familiarize practicing pathologists with the emerging cancer biomarkers and their diagnostic utilities. DATA SOURCES.: This review is based on the National Comprehensive Cancer Network guidelines and peer-reviewed English literature. CONCLUSIONS.: Tumor-specific biomarkers and molecular/genomic alterations, including pan-cancer markers, have been significantly expanded in the past decade thanks to large-scale high-throughput technologies and will continue to emerge in the future. These biomarkers can be of great value in diagnosis, prognosis, and/or targeted therapy/treatment. Familiarization with these emerging and ever-changing tumor biomarkers will undoubtedly aid pathologists in making accurate and state-of-the-art diagnoses and enable them to be more actively involved in the care of cancer patients.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Óseas/genética , Genómica , Neoplasias Hematológicas/genética , Trastornos Linfoproliferativos/genética , Técnicas de Diagnóstico Molecular , Neoplasias de los Tejidos Blandos/genética , Neoplasias Óseas/patología , Perfilación de la Expresión Génica , Neoplasias Hematológicas/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Trastornos Linfoproliferativos/patología , Valor Predictivo de las Pruebas , Neoplasias de los Tejidos Blandos/patología , TranscriptomaRESUMEN
PURPOSE OF REVIEW: Patient-derived tumor xenografts (PDTXs) have emerged as powerful platforms in medical oncology. A plethora of PDTXs were generated to study solid cancers, but limited data are as yet available on hematological diseases. The aim of this review is to describe the state of art of lymphoma PDTXs, discussing future directions for the development of integrated/personalized cancer programs. RECENT FINDINGS: In the last decades, several PDTXs of lymphoproliferative disorders have been produced. Most studies focused on acute lymphoblastic leukemias, but consistent results have recently been obtained also for indolent and aggressive B-/T-cell lymphomas. These models have contributed to characterize lymphoma biology and therapy, despite technical and scientific issues have partially limited their application (e.g. high costs, relatively low engraftment rates, lack of human-derived tumor microenvironment, clonal selection of engrafted cells, limited characterization of tumor grafts). In the next future, such limitations should be overcome by new technical approaches and dedicated multiinstitutional programs. SUMMARY: PDTXs represent an unprecedented opportunity to study the biology and clinical management of lymphoproliferative disorders. Many of the current models display limitations, which will be resolved by rigorous approaches and comprehensive libraries, recapitulating the extreme heterogeneity of such neoplasms.
Asunto(s)
Xenoinjertos , Trastornos Linfoproliferativos/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Antineoplásicos/farmacología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Linfoma/genética , Linfoma/inmunología , Linfoma/patología , Linfoma/terapia , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
Abstract Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents.
Resumo As doenças reumáticas juvenis afetam o sistema musculoesquelético e se iniciam antes dos 18 anos. Apresentam etiologia variada, identificável ou desconhecida, porém as de natureza inflamatória autoimune têm sido associadas ao maior risco de desenvolvimento de neoplasias, independentemente do tratamento. Este artigo propõe avaliar, por meio de revisão sistemática da literatura de acordo com os critérios de qualidade Prisma (Preferred Reporting Items for Systematic Reviews and Meta- Analyses), o risco de câncer em pacientes com doenças reumáticas juvenis e sua associação com imunobiológicos. Os critérios descritos pela iniciativa Strengthening the Reporting of Observational Studies in Epidemiology foram usados para avaliar a qualidade metodológica individual dos artigos selecionados no presente estudo. Foram analisadas nove publicações, de 251 incialmente selecionadas. Houve aumento no risco de câncer na população com doença reumática juvenil comparada com a população em geral. A maioria dos cânceres especificados foi de natureza linfoproliferativa. Sete estudos não especificaram a terapêutica ou não definiram associação entre ela e o risco de câncer. Apenas um estudo sugeriu essa associação e observou maior risco em pacientes diagnosticados nos últimos 20 anos, período de advento de novas terapias. Um estudo constatou maior risco em uma população não tratada com imunobiológicos, sugeriu tratar-se da evolução natural da doença, e não do efeito adverso da terapêutica. Os estudos demonstram aumento no risco de malignidade associada a doenças reumáticas juvenis que pode estar relacionada à atividade da doença, e não especificamente ao tratamento com imunobiológicos.
Asunto(s)
Humanos , Niño , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Terapia Biológica , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/patología , Enfermedades Autoinmunes/patología , Enfermedades Reumáticas/patología , Linfoma/complicaciones , Linfoma/patología , Linfoma/tratamiento farmacológico , Trastornos Linfoproliferativos/tratamiento farmacológicoRESUMEN
Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents.
Asunto(s)
Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Terapia Biológica , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/patología , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Autoinmunes/patología , Niño , Humanos , Linfoma/complicaciones , Linfoma/tratamiento farmacológico , Linfoma/patología , Trastornos Linfoproliferativos/tratamiento farmacológico , Enfermedades Reumáticas/patologíaRESUMEN
PURPOSE: To evaluate safety and activity of perifosine and sorafenib combination therapy in patients with lymphoproliferative diseases. EXPERIMENTAL DESIGN: Patients with relapsed and refractory lymphoproliferative diseases received perifosine (50 mg twice daily) for 1 month. Patients achieving less than partial response (PR) after perifosine alone were administered the combination therapy [perifosine plus sorafenib (400 mg twice daily)] until progressive disease (PD) or unacceptable toxicity occurred. The pERK and pAKT in peripheral blood lymphocytes as well as serum cytokine levels were investigated as predictive biomarkers of response. RESULTS: Forty patients enrolled in this study. After 1 month of perifosine alone, 36 who achieved less than PR went on to combination therapy, whereas four patients with chronic lymphocytic leukemia (CLL) who achieved PR continued with perifosine alone for a median of 10 months (range, 4-21). The most common drug-related toxicities were grade 1-2 anemia (17%), thrombocytopenia (9%), diarrhea (25%), joint pain (22%), and hand-foot skin reaction (25%). Three patients experienced grade 3 pneumonitis. Eight patients (22%) achieved PR, 15 (42%) achieved stable disease, and 13 (36%) experienced PD. A 28% PR rate was recorded for 25 patients with Hodgkin lymphoma. Among all patients, median overall survival and progression-free survival were 16 and 5 months, respectively. Early reductions in pERK and pAKT significantly correlated with the probability of clinical response. CONCLUSIONS: Perifosine and sorafenib combination therapy is feasible with manageable toxicity and demonstrates promising activity in patients with Hodgkin lymphoma. The predictive value of pERK and pAKT should be confirmed in a larger patient cohort.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/patología , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores/sangre , Biomarcadores/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/metabolismo , Trastornos Linfoproliferativos/mortalidad , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Estadificación de Neoplasias , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Fosforilcolina/administración & dosificación , Fosforilcolina/análogos & derivados , Proteínas Proto-Oncogénicas c-akt/metabolismo , Recurrencia , Sorafenib , Resultado del Tratamiento , Adulto JovenRESUMEN
Hypopigmentation in cutaneous T-cell lymphoproliferative disease should not always be equated with hypopigmented mycosis fungoides (MF). A form of hypopigmented pre-lymphomatous T-cell dyscrasia falling under the designation of the so-called hypopigmented interface variant of T-cell dyscrasia has recently been proposed. The aim of the present study was to establish hypopigmented interface T-cell dyscrasia as its own entity apart from other T-cell dyscrasias and MF using a patient case series. Twenty four cases of hypopigmented interface T-cell dyscrasia were identified in the dermatopathology database of Weill Medical College of Cornell University. There were 17 females and seven males (mean age, 36 years). In children and adolescents, the patients were most commonly of African American extraction. Truncal photo-protected areas manifesting as large solitary patches or multiple smaller macules were characteristic; disease progression to MF occurred in only one patient. The lesions responded to topical steroids and light therapy. The pathology was defined by a cell poor interface associated with degeneration of keratinocytes and melanocytes, and by lymphocytes whose nuclei showed low-grade cerebriform atypia, and which expressed a significant reduction in CD7 and CD62L expression. In 50% of the cases, the implicated cell type was of the CD8 subset. Clonality was not identified. Hypopigmented interface T-cell dyscrasia is a distinct entity separate from and rarely progressive to MF.
Asunto(s)
Hipopigmentación/patología , Trastornos Linfoproliferativos/patología , Micosis Fungoide/patología , Neoplasias Cutáneas/patología , Linfocitos T/patología , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Piel/patología , Adulto JovenRESUMEN
Anemia is a common comorbidity of lymphoproliferative malignancies, especially in multiple myeloma. Blood transfusions and ESAs (erythropoiesis stimulating agents) are both possible treatment options, but the latter is often preferred because of the potential risks of unwanted side effects related to blood transfusions. Evidence is accumulating that the use of ESAs in above clinical conditions is safe and effective and not associated with an increase in mortality or serious adverse events. 69.1% of patients achieved a hemoglobin response defined as an increase in hemoglobin of>2g/dl while receiving ESAs and concomitant chemotherapy. If supplemented with iron the hemoglobin response rate can be increased and hence the total dosage and financial cost reduced. A hemoglobin response is often accompanied by an increase in quality of life. HYPO% (hypochromic erythrocytes<5%) is believed to be both a significant positive predictor for the Hb response and also an indicator for iron supplementation if⩾5%. Conventional biochemical markers like serum ferritin concentration and transferrin saturation are not reliable for this use. The effect of EPO stimulating agents as the predictor of the Hb response, quality of life, mortality and the potential adverse events are discussed.
Asunto(s)
Anemia , Eritropoyesis/efectos de los fármacos , Hematínicos/uso terapéutico , Neoplasias Hematológicas , Trastornos Linfoproliferativos , Anemia/sangre , Anemia/etiología , Anemia/mortalidad , Anemia/patología , Anemia/terapia , Transfusión Sanguínea , Femenino , Ferritinas/sangre , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/terapia , Hemoglobinas/metabolismo , Humanos , Hierro/sangre , Hierro/uso terapéutico , Trastornos Linfoproliferativos/sangre , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/terapia , Masculino , Calidad de VidaRESUMEN
A case of lymphoid hyperplasia arising in the large intestine of a 54-year-old woman is described. Barium enema X-ray and colonoscopic examination revealed multiple small polyps in the right side of the colon. Pathological findings from forceps biopsy revealed similar features to a mucosa-associated lymphoid tissue (MALT) lymphoma. A right hemicolectomy with mesenteric lymph node dissection was carried out. Histological sectioning demonstrated hypertrophic lymphoid follicles with well-formed germinal centers. Occasionally, lymphocytes infiltrated the crypts, in a way similar to that found in lymphoepithelial lesions, which was suggestive of a MALT lymphoma diagnosis. Cryptitis was also observed in the lamina propria. Immunohistochemically, proliferating lymphocytes were positive for CD20 (L26) and negative for CD45RO (UCHL-1). Analyses of immunoglobulin gene (IgHJH) rearrangement could not detect any monoclonality in these cells. These findings suggested that the present case should be categorized as lymphoid hyperplasia rather than lymphoma.
Asunto(s)
Colon/patología , Pólipos Intestinales/patología , Ganglios Linfáticos/patología , Trastornos Linfoproliferativos/patología , Antígenos CD20/metabolismo , Colon/metabolismo , Colon/cirugía , ADN/análisis , Diagnóstico Diferencial , Femenino , Reordenamiento Génico , Genes de Inmunoglobulinas/genética , Humanos , Hiperplasia/patología , Pólipos Intestinales/genética , Pólipos Intestinales/metabolismo , Cariotipificación , Escisión del Ganglio Linfático , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/cirugía , Linfoma de Células B de la Zona Marginal/diagnóstico , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/metabolismo , Persona de Mediana EdadRESUMEN
AIMS: To describe and illustrate a novel and highly sensitive peroxidase-based immunohistochemical detection system which employs mutually attractive, mirror image complementary antibodies (MICA). METHODS AND RESULTS: To demonstrate the sensitivity of the MICA system alongside the avidin-biotin complex (ABC) method, we selected a range of mouse monoclonal and rabbit polyclonal primary antibodies against antigens that are generally regarded as relatively difficult or impossible to detect on formalin-fixed, paraffin-embedded lymphoid tissue. Compared with the ABC method, the MICA immunodetection method enabled us to dilute primary antibodies up to 200-fold with equivalent or superior immunostaining results and, usually, considerably shortened primary antibody incubation times. CONCLUSIONS: We have described and illustrated a novel immunohistochemical detection system and demonstrated greatly increased sensitivity over the commonly used ABC system. An additional advantage of the MICA system is that it is avidin-free and so avoids non-specific staining due to endogenous tissue biotin.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos de Neoplasias/análisis , Técnicas para Inmunoenzimas/métodos , Animales , Antígenos Virales/análisis , Células Dendríticas/química , Células Dendríticas/patología , Infecciones por Herpesviridae/patología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Linfoma Folicular/química , Linfoma Folicular/patología , Linfoma Anaplásico de Células Grandes/química , Linfoma Anaplásico de Células Grandes/patología , Linfoma no Hodgkin/química , Linfoma no Hodgkin/patología , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/virología , Ratones , Tonsila Palatina/química , Tonsila Palatina/patología , Complicaciones Posoperatorias , Conejos , Sensibilidad y Especificidad , Infecciones Tumorales por Virus/patologíaRESUMEN
Therapeutic effects of combined treatment with a Chinese medicine prescription, Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT) and suboptimal doses of prednisolone (PSL) on pathological findings of autoimmune-prone MRL/lpr mice were examined. Six-week-old MRL/lpr mice were treated orally with 1000 mg/kg of NYT, 0.5 or 2 mg/kg of PSL, 1000 mg/kg of NYT plus 0.5 or 2 mg/kg of PSL (combined treatment) or solvent only (control) six times per week. The rates of signs and symptoms of autoimmune disease (lymphadenopathy, proteinuria, dermatitis, loss of hair) were suppressed significantly in groups given PSL (2 mg/kg) alone, NYT alone and combined treatment with PSL (2 mg/kg) plus NYT (1000 mg/kg) compared with control, respectively, whereas treatment with PSL (0.5 mg/kg) alone did not inhibit their occurrence. ConA response and IL-2 production were also improved significantly in lymphocytes of mice given the combined treatment. Interestingly, treatment with NYT alone enhanced further the augmented IFN-gamma production in MRL/lpr mice but the combined treatment suppressed such an augmented production. The combined treatment dramatically reduced the level of anti-DNA antibodies in serum of MRL/lpr mice. By contrast, NYT alone treatment had no effect on autoantibodies production. These results suggest that combined treatment with NYT plus a suboptimal dose of PSL could be effective for systemic lupus erythematosus without severe side-effects.
Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Trastornos Linfoproliferativos/tratamiento farmacológico , Prednisolona/administración & dosificación , Animales , Anticuerpos Antinucleares/análisis , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , ADN/inmunología , Quimioterapia Combinada , Femenino , Interferón gamma/biosíntesis , Activación de Linfocitos , Tejido Linfoide/efectos de los fármacos , Tejido Linfoide/patología , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/patología , Masculino , Ratones , Ratones Endogámicos C3HRESUMEN
The chemopreventive action of carotenoids on proteinuria and lymphadenopathy were examined in autoimmune-prone MRL-lpr/lpr (MRL/l) mice. They were fed a synthetic full-fed diet (16-18 kcal/mouse/day) with supplementation of beta-carotene or astaxanthin (0.19 mumoles/mouse, 3 times a week), and the development of lymphadenopathy and proteinuria were examined. MRL/l mice fed a full-fed diet without the supplementation of carotenoids or those fed a calorie-restricted (CR) diet (10-11 kcal/mouse/day, 60% calorie intake of full-fed mice) were employed as controls. CR dramatically delayed the development of proteinuria and lymphadenopathy, as reported previously. Carotenoids also significantly delayed the onset of these symptoms in MRL/l mice fed a full-fed diet. Carotenoids were half as effective as CR and astaxanthin, a carotenoid without provitamin A activity, which appeared to exert more significant preventive actions than beta-carotene in delaying the development of these symptoms. Similar chemopreventive actions of carotenoids were also demonstrated in MRL/l mice fed a regular diet (Lab Chow). CR has been shown to augment IL-2 production and to decrease serum prolactin levels in this strain, which may be related to its dramatic preventive action of autoimmunity. However, carotenoids did not affect IL-2 production nor prolactin levels in full-fed MRL/l mice. The chemopreventive actions of carotenoids observed in autoimmune-prone MRL/l mice may be attributed to yet unknown mechanisms, apart from their provitamin A activity or oxygen-quenching activity.
Asunto(s)
Enfermedades Autoinmunes/prevención & control , Carotenoides/uso terapéutico , Trastornos Linfoproliferativos/prevención & control , Ratones Mutantes/inmunología , Proteinuria/prevención & control , Animales , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/patología , Peso Corporal/efectos de los fármacos , Carotenoides/farmacología , Dieta Reductora , Ingestión de Energía , Femenino , Alimentos Fortificados , Interleucina-2/biosíntesis , Ganglios Linfáticos/patología , Activación de Linfocitos/efectos de los fármacos , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/patología , Ratones , Tamaño de los Órganos/efectos de los fármacos , Prolactina/sangre , Proteinuria/etiología , Proteinuria/patología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Xantófilas , beta CarotenoRESUMEN
MRL-lpr/lpr mice were treated with Tripterygium Wilfordii Hook-F (TWHF), a Chinese herbal medicine successfully used for human rheumatoid arthritis. Dramatic prolongation of survival and the reduction of urinary protein were observed in mice treated with a high dose of TWHF (20 mg/kg, three times a week) compared to the control animals receiving solvent alone. A slight but significant reduction was also seen in the degree of lymphadenopathy and arthritis with the high dose treatment. Surprisingly, no significant difference was present in IgM rheumatoid factor and IgG anti-double-stranded DNA antibody levels or in the histopathology of lupus nephritis. These results indicate the dissociation of histopathological renal disease and the degree of proteinuria or the life span. Although further pharmacological analysis is required, TWHF might be potentially useful for diseases such as systemic lupus erythematosus or nephrotic syndrome.