RESUMO
Background: Penile tumors are rare in dogs and only single case reports or small case series have been reported. Case description: An 11-year-old, cross-breed dog was presented for a two-week history of stranguria. At physical examination, a subcutaneous swelling of the penis was detected. Abdominal radiographs, ultrasonography, and CT showed a subcutaneous penile mass involving the penile urethra and bulbus glandis associated with marked lysis of the os penis. Histological features along with the neoplastic cell positivity to CD31 and FVIII immunohistochemical markers warranted a final diagnosis of penile hemangiosarcoma. Findings/treatment and outcome: The dog was treated with amputation of the penis, scrotal urethrostomy, and five adjuvant doses of doxorubicin along with thalidomide. Cutaneous and omental metastases were found 235 days after surgery. The dog was euthanized at 296 days due to bone and pulmonary metastasis. Conclusion: Penile hemangiosarcoma seems to share the same aggressive behavior with other hemangiosarcomas seen in other anatomical locations. Therefore, surgery and chemotherapy may improve survival time in dogs with penile hemangiosarcoma as well.
RESUMO
BACKGROUND: The Human Papillomavirus (HPV) has different strategies for persist in the cells. This characteristic has led us to consider the presence of the virus in tissues of the oral cavity that had no clinical signs of infection. The aim of this study was to detect the presence of DNA-HPV at multiple sites of the oral cavity. MATERIAL AND METHODS: A case-control study was designed: Oral Squamous Carcinoma Group (OSCG), healthy n=72 and Control Group (CG), n=72, healthy volunteers paired by sex and age with OSCG. Four samples were taken from OSCG: saliva, biopsy, brush scraping of lesion and contralateral healthy side. In CG a saliva sample and a scratch of the posterior border of tongue were collected. HPV was detected by PCR using Bioneer Accuprep genomic DNA Extraction kit, and consensus primers MY09 and MY11. Chi square test was applied. RESULTS: 432 samples were obtained from 144 individuals. DNA-HPV was detected in 30 (42%) of OSCG subjects and 3(4%) of CG. Two or more positive samples were obtained in 67% of the OSCG, 67% in saliva and 60% in biopsy; in CG 100% of the individuals were positive in the two samples. CONCLUSIONS: HPV is frequently present in oral cavity as a multifocal infection, even without the presence of clinical lesions.
Assuntos
Neoplasias Bucais , Papillomaviridae , Infecções por Papillomavirus , Estudos de Casos e Controles , DNA Viral , HumanosAssuntos
Biomarcadores/sangue , Eritropoetina/sangue , Síndromes Mielodisplásicas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Células Precursoras Eritroides/patologia , Feminino , Hematínicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológicoRESUMO
BACKGROUND: Allogeneic stem-cell transplantation (HSCT) is the only curative treatment in myelodysplastic syndromes (MDS). Azacitidine (AZA) is increasingly used prior to HSCT, however in Europe it is only approved for patients who are not eligible for HSCT. PATIENTS AND METHODS: We conducted a phase II multicenter study to prospectively evaluate the feasibility of HSCT after treatment with AZA in 70 patients with a myelodysplastic syndrome (MDS), 19 with acute myeloid leukemia (AML), and 8 with chronic myelomonocytic leukemia (CMML). After a median of four cycles (range 1-11): 24% of patients achieved complete remission, 14% partial remission, 8% hematologic improvement, 32% had stable and 22% progressive disease. Ten patients discontinued treatment before the planned four cycles, due to an adverse event in nine cases. RESULTS: A HSC donor was identified in 73 patients, and HSCT was performed in 54 patients (74% of patients with a donor). Main reasons for turning down HSCT were lack of a donor, an adverse event, or progressive disease (9, 12, and 16 patients, respectively). At a median follow-up of 20.5 months from enrolment, response to AZA was the only independent prognostic factor for survival. Compared to baseline assessment, AZA treatment did not affect patients' comorbidities at HSCT: the HCT-CI remained stable in 62% patients, and worsened or improved in 23% and 15% of patients, respectively. CONCLUSIONS: Our study shows that HSCT is feasible in the majority of patients with HR-MDS/AML/CMML-2 after AZA treatment. As matched unrelated donor was the most frequent source of donor cells, the time between diagnosis and HSCT needed for donor search could be 'bridged' using azacitidine. These data show that AZA prior to HSCT could be a better option than intensive chemotherapy in higher-risk MDS. The trial has been registered with the EudraCT number 2010-019673-1.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Azacitidina/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Leucemia Mielomonocítica Crônica/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Estudos de Viabilidade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Itália , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Leucemia Mielomonocítica Crônica/mortalidade , Leucemia Mielomonocítica Crônica/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Tumor lysis syndrome (TLS) is a rare but potentially life-threatening complication of neoplasms, preferentially hematological malignancies. Well known since at least ninety years ago, this condition can be misdiagnosed and incorrectly managed due to rapid onset of symptoms, sometimes overlapping with cancer-derived clinical conditions. Our purpose is to discuss some old and new issues of this syndrome. Predisposing factors as type of malignancy, chemotherapy regimen and age are promptly available and useful tools for inducing TLS suspicion. Management of clinical syndrome requires hydration, fluid balance, electrolytes and hyperuricemia correction, and ultimately dialysis when acute kidney injury is worsening.
Assuntos
Neoplasias/complicações , Síndrome de Lise Tumoral/etiologia , Síndrome de Lise Tumoral/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Gerenciamento Clínico , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/prevenção & controleAssuntos
Anemia de Fanconi/genética , Leucemia Mieloide Aguda/genética , Segunda Neoplasia Primária/genética , Adulto , Idoso , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Análise de Sequência de DNARESUMO
Higher-risk myelodysplastic syndromes (MDS) are rarely curable and have a poor prognosis. We investigated the accuracy of physicians' perception of patients' health status and the patients' preferences for involvement in treatment decisions. We examined 280 newly diagnosed higher-risk elderly MDS patients paired with their physicians. Survey tools included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the Control Preference Scale. Overall concordance was 49% for physician perception of patient preferences for involvement in treatment decisions. In 36.4% of comparisons there were minor differences and in 14.6% there were major differences. In 44.7% of the patients preferring a passive role, physicians perceived them as preferring an active or collaborative role. Absence of the patient's request for prognostic information (P=0.001) and judging the patient as having a poor health status (P=0.036) were factors independently associated with the physicians' attitude toward a lower degree of patient involvement in clinical decisions. Agreement on health status was found in 27.5% of cases. Physicians most frequently tended to overestimate health status of patients who reported low-level health status. The value of decision aid-tools in the challenging setting of higher-risk MDS should be investigated to further promote patient-centered care.
Assuntos
Nível de Saúde , Síndromes Mielodisplásicas/terapia , Preferência do Paciente , Relações Médico-Paciente , Médicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/psicologia , Participação do Paciente/psicologia , Participação do Paciente/estatística & dados numéricos , Preferência do Paciente/estatística & dados numéricos , Percepção , Médicos/psicologia , Médicos/estatística & dados numéricos , Qualidade de Vida , Fatores de Risco , Inquéritos e QuestionáriosAssuntos
Epigênese Genética , Leucemia Mieloide Aguda/genética , Leucemia/genética , Mutação , Transtornos Mieloproliferativos/patologia , Spliceossomos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Mieloide Aguda/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Azacitidina/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Aprovação de Drogas , Humanos , Masculino , Fatores de TempoAssuntos
Azacitidina/uso terapêutico , Metilação de DNA , Proteínas de Ligação a DNA/genética , Mutação/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Dioxigenases , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Hypomethylating drugs are useful in the management of Myelodysplastic syndromes, but there are only few reports on chronic myelomonocycitic (CMML) leukemia patients. We describe our experience in 3 CMML patients treated with azacitidine. Two patients obtained partial response after 4 treatment cycles with only minor toxicity and are in continuous partial response, with stable peripheral blood counts, at 29 and 30 cycles from treatment start.
RESUMO
BACKGROUND: Our objective was to assess the relative bioavailability of the first somatropin produced in transgenic cloned cows that carry the human growth hormone (GH) gene (Biohormon) and somatropin produced in Escherichia coli culture (HHT), the procedure most frequently used for the commercial production of the hormone. METHODS: Upon approval by an independent ethics committee and the National Regulatory Agency of Argentina, we compared the time-concentration profiles of somatropin in 24 healthy volunteers, in a randomized, 2-period, 2-sequence crossover design after inhibition of endogenous GH secretion with lanreotide, a long-acting somastostatin analogue. After the subcutaneous administration of 1.33 mg of each formulation, serum somatropin was analyzed by chemiluminescent immunoassay and IGF-I by immunoradiometric assay. Safety was assessed by clinical and laboratory parameters. Pharmacokinetic parameters were calculated with Win Nonlin 5.2 using a non-compartmental model and bioequivalence was assessed. RESULTS: The test/reference ratios of AUC, AUC(last) and C(max) were 106.4 (90% CI = 100.2-112.9), 105.3 (90% CI = 99.1-111.8) and 105.49 (90% CI = 92.6-120.1), respectively. No serious adverse events were reported and no GH antibodies were detected. CONCLUSION: This study demonstrates that a single dose of Biohormon, the first product with somatropin obtained from milk of transgenic mammals, is bioequivalent to the reference product HHT according to standard criteria.
Assuntos
Hormônio do Crescimento/farmacocinética , Proteínas Recombinantes/farmacocinética , Adulto , Animais , Animais Geneticamente Modificados , Área Sob a Curva , Disponibilidade Biológica , Bovinos , Estudos Cross-Over , Nanismo Hipofisário/metabolismo , Nanismo Hipofisário/terapia , Feminino , Hormônio do Crescimento/biossíntese , Hormônio do Crescimento/sangue , Meia-Vida , Terapia de Reposição Hormonal/métodos , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Leite/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/sangueRESUMO
BACKGROUND: Levels of cell-free circulating DNA have been correlated to clinical characteristics and prognosis in patients with cancers of epithelial origin, while there are no data on patients with B-lymphoproliferative diseases. PATIENTS AND METHODS: Cell-free DNA levels in the plasma samples of 142 patients with lymphomas [45 with Hodgkin's lymphoma (HL), 63 with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL), 24 with follicular, and 10 with mantle cell non-Hodgkin's lymphoma (NHL)] at diagnosis and of 41 healthy individuals were determined using a quantitative PCR for the beta-globin gene. RESULTS: Levels of circulating DNA in patients with HL, DLBCL, and mantle cell NHL were significantly higher than in controls (P < 0.01 for all). Increased levels of plasma DNA were associated with advanced stage disease, presence of B-symptoms, elevated lactate dehydrogenase levels, and age >60 years (P = 0.009; <0.0001; <0.0001; 0.04, respectively). In HL, histological signs of necrosis and grade 2 type of nodular sclerosis were associated with increased plasma DNA. Elevated plasma DNA levels were associated with an inferior failure-free survival in patients with HL (P = 0.01) and DLBCL (P = 0.03). CONCLUSION: Quantification of circulating DNA by real-time PCR at diagnosis can identify patients with elevated levels that are associated with disease characteristics indicating aggressive disease and poor prognosis.
Assuntos
DNA de Neoplasias/sangue , Doença de Hodgkin/genética , Linfoma Difuso de Grandes Células B/genética , Adulto , Idoso , DNA de Neoplasias/genética , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/patologia , Humanos , Modelos Logísticos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Adulto Jovem , Globinas beta/genéticaRESUMO
OBJECTIVES: To characterize the IFNbeta1a-regulated gene expression on leukocytes of Multiple Sclerosis (MS) patients using microarrays with whole human genome representation. METHODS: Genes differentially expressed by interferon-beta were identified by a microarray in vitro study performed in leukocytes obtained from 5 MS relapsing-remitting patients. RESULTS: Following the culture of peripheral blood mononuclear cells from MS relapsing-remitting patients for 24 hs with IFNbeta1a, the expression of 868 genes was modified: 545 increased (including CXCL11, CCL8, INDO, IFI27, CFB, CXCL10 and IFIT1) and 323 diminished (including RBP7, SEPT5, RNF8, ADORA2B and FOS). CONCLUSIONS: Since many of them were previously recognized as involved in MS pathogenesis, the IFNbeta1a mechanism of action could imply a compensatory regulation of systems deregulated in MS.
Assuntos
Adjuvantes Imunológicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Interferon beta/farmacologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Adulto , Feminino , Perfilação da Expressão Gênica/métodos , Genoma Humano , Humanos , Técnicas In Vitro , Interferon beta-1a , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
Vascular endothelial growth factor (VEGF) gene transfer-mediated angiogenesis has been proposed for peripheral artery disease. However, protocols using single administration have shown little benefit. Given that the transient nature of VEGF gene expression provokes instability of neovasculature, we hypothesized that repeated administration would provide efficient tissue protection. We thus compared single vs repeated transfection in a rabbit model of hindlimb ischemia by injecting a plasmid encoding human VEGF165 (pVEGF165) at 7 (GI, n=10) or 7 and 21 (GII, n=10) days after surgery. Placebo animals (GIII, n=10) received empty plasmid. Fifty days after surgery, single and repeated administration similarly increased saphenous peak flow velocity and quantity of angiographically visible collaterals. However, microvasculature increased only with repeated transfection: capillary density was 49.4+/-15.4 capillaries per 100 myocytes in GI, 84.6+/-14.7 in GII (P<0.01 vs GI and GIII) and 49.3+/-13.6 in GIII, and arteriolar density was 1.9+/-0.6 arterioles per mm2 in GI, 3.0+/-0.9 in GII (P<0.01 vs GI and GIII) and 1.5+/-0.6 in GIII. Muscle lesions were reduced only within repeated transfection. With single administration, gene expression peaked at 7 days and declined rapidly, but with repeated administration, it remained positive at 50 days. At 90 days of repeated transfection (additional animals), gene expression decreased significantly, but neovessel densities did not. Thus, repeated, but not single, VEGF gene transfection resulted in increased microvasculature, which, in turn, afforded effective protection against ischemic muscle damage.
Assuntos
Terapia Genética/métodos , Isquemia/terapia , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica , Doenças Vasculares Periféricas/terapia , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Modelos Animais de Doenças , Expressão Gênica/fisiologia , Técnicas de Transferência de Genes , Membro Posterior/irrigação sanguínea , Humanos , Injeções Intramusculares , Isquemia/etiologia , Microvasos/diagnóstico por imagem , Doenças Vasculares Periféricas/complicações , Plasmídeos , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Coelhos , Radiografia , Fluxo Sanguíneo Regional/fisiologia , Fatores de Tempo , Transfecção , Transgenes , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The impact of endocrine therapies in the adjuvant treatment of premenopausal patients with early breast cancer is well established. However, the right combination and duration of endocrine manipulations currently available (luteinizing hormone-releasing hormone analogs and tamoxifen) remain unclear. Moreover, the role of chemotherapy in addition to endocrine therapies is not clearly defined. The most recent Early Breast Cancer Trialists' Collaborative Group overview has confirmed the efficacy of five years of tamoxifen in reducing the annual recurrence rate and the annual breast cancer death rate by 41 and 34%, respectively, in an estrogen receptor-positive population. These results are largely irrespective of age, use of chemotherapy or other tumor features. Moreover, the expert panel of the St. Gallen Conference accepted both tamoxifen or tamoxifen plus ovarian suppression as standard endocrine therapy for premenopausal breast cancer patients with endocrine-responsive disease. The use of ovarian suppression or ablation also significantly reduced the risk of breast cancer-related death, mainly in the absence of other systemic therapies. Chemotherapy is widely used in this population; however, its role in endocrine-positive premenopausal women with hormone-positive disease treated with optimal endocrine therapy remains unclear.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Sistema Endócrino/efeitos dos fármacos , Pré-Menopausa , Quimioterapia Adjuvante , Feminino , HumanosRESUMO
OBJECTIVES: Recombinant human interferon-beta (IFN-b) is a well-established treatment for multiple sclerosis (MS). The regulatory process for marketing authorization of biosimilars is currently under debate in certain countries. In the EU, EMEA has clearly defined the process including overarching and product-specific guidelines, which includes clinical testing. Biosimilarity needs to be based on comparability criteria, including at least molecular characterization, biological activity relevant for the therapeutic effect and relative bioavailability ("bioequivalence"). In the case of such complex diseases as MS, where the effect of treatment is not so directly measurable, in vitro tools can provide additional data to support comparability. Genomic microarrays assays might be useful to compare multisource biopharmaceuticals. The aim of the present study was to compare the pharmacodynamic genomic effects (in terms of transcriptional regulation) of two recombinant human IFN-I(2)1a preparations on lymphocytes of multiple sclerosis patients using a whole genome microarray assay. METHODS: We performed an ex vivo whole genome expression profiling of the effect of two preparations of IFN-I(2)1a on non-adherent mononuclears from five relapsing-remitting MS patients analyzing microarrays (CodeLink Human Whole Genome). Patients blood was drawn, PBMCs isolated and cultured in three different conditions: culture medium (control), 1,000 U/ml of IFN-I(2)1a (BLA- (STOFERON, Bio Sidus) and 1,000 U/ml of IFN-I(2)1a (REBIF, Serono) RNA was purified from non-adherent cells (mostly lymphocytes), amplified and hybridized. Raw data were generated by CodeLink proprietary software. Data normalization, quality control and analysis of differential gene expression between treatments were done using linear model for microarray data. Functional annotation analysis of IFN-I(2)1a MS treatment transcription was done using DAVID. RESULTS: Out of the approximately 45,000 human sequences examined, no evidence of differential regulation was found when both treatments were compared (minimum adjusted p-value > 0.999). The IFN-I(2)1a effect differentially regulated the expression of 868 genes. The expression of standard markers such as GTP cyclohidrolase, MxA, and OAS isoenzymes A and B changed as a consequence of the action of IFN-I(2)1a. CONCLUSIONS: This exhaustive and highly sensitive assay did not show differences in the genomic expression profile of these two products under the assayed experimental conditions. These results suggest that this technology might be useful for the initial comparison of biosimilars, being part of a comprehensive comparability program that includes clinical testing.
Assuntos
Perfilação da Expressão Gênica , Interferon beta/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Transcrição Gênica/efeitos dos fármacos , Análise por Conglomerados , Biologia Computacional/métodos , Composição de Medicamentos/métodos , Feminino , Genoma Humano , Humanos , Interferon beta-1a , Interferon beta/genética , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Fanconi anemia (FA) is an autosomal recessive disease characterized by pancitopenia, congenital malformations, predisposition to cancers and chromosomal instability. We report the clinical and molecular features of a patient initially identified as a potential FA case only because of chemotherapy toxicity during the treatment of a T-lineage acute lymphoblastic leukemia (ALL). Cells from this patient showed a moderate chromosomal instability, increasing sensitivity to DNA crosslinking agents but normal response to ionizing radiation. The analysis of FA proteins demonstrated a marked reduction of FANCD2 (>95%), but normal levels of FANCA or FANCG. Interestingly, this defect was associated with a homozygous missense mutation of FANCD2, resulting in a novel amino-acid substitution (Leu153Ser) at residue Leu153, which is highly conserved through evolution. The FANCD2(L153S) protein, whose reduced expression was not due to impaired transcription, was detected also in its monoubiquitinated form in the nucleus, suggesting that the mutation does not affect post-translation modifications or subcellular localization but rather the stability of FANCD2. Therefore, the hypomorphic Leu153Ser mutation represents the first example of a FANCD2 defect that might promote clonal progression of tumors, such as T-ALL, and severe chemotherapy toxicity in patients without any clinical manifestations typical of FA.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/genética , Mutação , Substituição de Aminoácidos , Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Antígenos CD13 , Criança , Instabilidade Cromossômica , Progressão da Doença , Anemia de Fanconi/genética , Humanos , Infecções/etiologia , Infecções/genética , Leucemia-Linfoma de Células T do Adulto/fisiopatologia , Masculino , Pancitopenia/induzido quimicamente , Pancitopenia/genética , Indução de Remissão , Lectina 3 Semelhante a Ig de Ligação ao Ácido SiálicoRESUMO
We have recently reported that in pigs with chronic myocardial ischemia heart transfection with a plasmid encoding the 165 isoform of human vascular endothelial growth factor (pVEGF165) induces an increase in the mitotic index of adult cardiomyocytes and cardiomyocyte hyperplasia. On these bases we hypothesized that VEGF gene transfer could also modify the evolution of experimental myocardial infarct. In adult sheep pVEGF165 (3.8 mg, n=7) or empty plasmid (n=7) was injected intramyocardially 1 h after coronary artery ligation. After 15 days infarct area was 11.3+/-1.3% of the left ventricle in the VEGF group and 18.2+/-2.1% in the empty plasmid group (P<0.02). The mechanisms involved in infarct size reduction (assessed in additional sheep at 7 and 10 days after infarction) included an increase in early angiogenesis and arteriogenesis, a decrease in peri-infarct fibrosis, a decrease in myofibroblast proliferation, enhanced cardiomyoblast proliferation and mitosis of adult cardiomyocytes with occasional cytokinesis. Resting myocardial perfusion (99mTc-sestamibi SPECT) was higher in VEGF-treated group than in empty plasmid group 15 days after myocardial infarction. We conclude that plasmid-mediated VEGF gene transfer reduces myocardial infarct size by a combination of effects including neovascular proliferation, modification of fibrosis and cardiomyocyte regeneration.