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1.
Gan To Kagaku Ryoho ; 48(11): 1397-1399, 2021 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-34795134

RESUMO

Reports of multiple cancer cases are increasing with the improvement of diagnostic techniques and the extension of life expectancy. In addition, the increase in the prevalence of multiple cancers is expected because the increase in the prevalence of juvenile breast cancer has been a concern in recent years. Particularly, in the case of simultaneity, the problem is how much treatment priority and curability should be sought depending on the stage and prognosis of each tumor. We report a case of malignant lymphoma and colon cancer that occurred during breast cancer treatment.


Assuntos
Neoplasias da Mama , Neoplasias do Colo , Linfoma , Neoplasias Primárias Múltiplas , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Feminino , Humanos , Linfoma/terapia , Prognóstico
2.
J Pak Med Assoc ; 71(Suppl 5)(8): S83-S86, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34634023

RESUMO

OBJECTIVE: To determine the experience at the Aga Khan University Hospital in diagnosing and treating adult patients with primary lymphoma of bone. Methodology: All patients with Primary lymphoma of bone (PLB) that were diagnosed and/or treated at Aga Khan University Hospital, Karachi from 2005 to 2019 were included as part of this study. RESULTS: There were 17 patients with PLB including 13 (76.5%) males and 4 (23.5%) females with a mean age of 44 ± 16.5 years. Nine patients were between 30-59 years of age at diagnosis. The mean follow-up time of patients was 80±46.7 months. Six patients had tumours of pelvic bone followed by tibia (5) and femur (4). Four patients had a pathological fracture at the time of presentation whereas 2 (11.8%) required surgical fixation of the pathological fracture. The stage of the tumour was based on Ann Arbor classification. Nine (52.9%) cases had Stage 1 disease, 7 (41.2%) had stage IV disease with metastasis in extra nodal tissues. As for treatment, every patient received chemotherapy whereas 5 (29.4%) received adjuvant radiotherapy. Complete remission in the size of the tumour was seen in 11 (64.7%) patients while 6 (35.3%) had partial remission. Post-treatment, 4 (23.5%) patients expired. The mean Overall Survival (OS) time was 80.18 ± 46.71months with a survival rate of 76.5. CONCLUSIONS: Primary lymphoma of the bone can be treated with medical regime and good prophylactic surgeries to avoid pathological fracture such as intramedullary nailing.


Assuntos
Linfoma , Adulto , Estudos Transversais , Feminino , Hospitais Universitários , Humanos , Linfoma/epidemiologia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária
3.
Ann Transplant ; 26: e933365, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34635633

RESUMO

BACKGROUND High-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) plays a crucial role in the therapy of patients with lymphoma. This retrospective study aimed to analyze prognostic factors in patients undergoing HDT/ASCT for lymphoma. MATERIAL AND METHODS We included patients with lymphoma who underwent HDT/ASCT at our center. Time-to-event outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed with the Kaplan-Meier method and log-rank test. Receiver operating characteristic (ROC) curve analysis and Cox proportional hazard regression analysis were performed to explore the prognostic value of different factors. RESULTS A total of 113 patients with lymphoma were included. Patients with low serum albumin levels (<37 g/L) before transplantation had significantly lower PFS and OS (P<0.01). Albumin levels before transplantation significantly predicted early progression (progressed within 1 year) after transplantation (AUC=0.706, P=0.003). Multivariate Cox analysis indicated that low albumin level (hazard ratio [HR] 3.19, 95% confidence interval [CI] 1.54-6.63; P=0.002) and age >60 years (HR 2.92, 95% CI 1.27-6.71; P=0.012) were independent risk factors for PFS. Total protein <60 g/L was an independent risk factor for OS (HR 3.57, 95% CI 1.45-8.78; P=0.006). CONCLUSIONS Low albumin level before transplantation was an independent risk factor in patients with lymphoma undergoing HDT/ASCT. Intense care and effective maintenance therapy after transplantation are required for patients with low albumin levels.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Albumina Sérica Humana/análise , Humanos , Linfoma/terapia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Autólogo
4.
Brain Nerve ; 73(10): 1067-1074, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34615743

RESUMO

What are desirable roles of general neurologists in the diagnosis and treatment of primary central nervous system lymphoma (PCNSL)? These issues were discussed 7 years back in the special feature articles of this journal. In the last 7 years genome analyses using liquid biopsy specimens have progressed and are becoming popular in the management of PCNSL, thereby enabling neurosurgeons to avoid invasive brain biopsy. The role of general neurologists in this country is not to be directly engaged in the PCNSL management, but to make an early diagnosis of PCNSL and to refer patients with PCNSL to specialists for a combination of chemotherapy and irradiation therapy.


Assuntos
Linfoma , Neurologistas , Sistema Nervoso Central , Humanos , Linfoma/diagnóstico , Linfoma/terapia
5.
Brain Nerve ; 73(10): 1107-1114, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34615748

RESUMO

Management of primary central nervous system lymphoma (PCNSL) includes induction and consolidation therapies in newly diagnosed patients, as well as second-line therapy in relapsed or refractory patients. The current standard-of-care induction therapy involves methotrexate (MTX)-based multi-agent immunochemotherapy with rituximab, methotrexate, procarbazine, and vincristine. Deferral or dose reduction of radiation therapy is considered in consolidation therapy, especially in elderly patients who carry a high risk of radiation-induced delayed neurotoxicity. Since elderly patients comprise the main population of PCNSL, minimally toxic treatments that are effective and feasible for them are strongly needed. For second-line therapy, rechallenge using MTX-based chemotherapy (in patients with a prior durable response to MTX-based chemotherapy) or radiation therapy is considered. Bruton's tyrosine kinase inhibitor tirabrutinib (for relapsed and refractory PCNSL) and high-dose chemotherapy with autologous stem cell transplantation support using thiotepa and busulfan (BuTT) were approved by the Japanese Ministry of Health and Welfare in March 2020 and has recently become available for clinical practice. While these novel treatments seem promising, the optimal use of these treatments along with the standard-of-care therapy of PCNSL should be defined and investigated in clinical trials.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Idoso , Sistema Nervoso Central , Humanos , Japão , Linfoma/terapia , Transplante Autólogo
6.
Curr Oncol ; 28(5): 3891-3899, 2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34677250

RESUMO

Manifestation of malignant lymphoma in the spine is rare; there have only been a few cases reported in the literature. Due to its rarity, there is no gold standard for the management of patients suffering from spinal lymphoma manifestations. Methods: We retrospectively reviewed the data for 37 patients (14 female, 23 male) with malignant lymphoma in the spine receiving intervention in our center from March 2006 until June 2020. Neurological impairment, pain, diagnostics, and/or surgical instability were the criteria for surgery in this patient cohort. Otherwise, only CT-guided biopsies were conducted. Analysis of the patient cohort was based on the Karnofsky performance status scale (KPSS), location of the lesion, spinal levels involved, spinal instability neoplastic score (SINS), surgical treatment, histopathological workup, adjuvant therapy, and overall survival. The following surgical procedures were performed: posterior stabilization and decompression in nine patients; decompression and/or tumor debulking in 18 patients; a two-staged procedure with dorsal stabilization and vertebral body replacement in four patients; decompression and biopsy in one patient; a two-stage procedure with kyphoplasty and posterior stabilization for one patient; posterior stabilization without decompression for one patient; a vertebroplasty and cement-augmented posterior stabilization for one patient; and a CT-guided biopsy alone for two patients. Twenty-one patients (56.78%) had ≥1 lesion in the thoracic spine, 10 patients (27.03%) had lesions in the lumbar spine, two patients had lesions in the cervicothoracic junction, two patients had lesions in the thoracolumbar junction, one patient had a lesion in the lumbosacral junction, and one patient had a lesion in the sacrum. The diagnoses of the histopathological workup were diffuse large B-cell lymphoma in 23 (62.16%) cases, indolent lymphoma in 11 (29.74%) cases, anaplastic T-cell lymphoma in one case (2.70%), T-cell lymphoma in one case (2.70%), and Burkitt lymphoma in one (2.70%) case. The median overall survival was 7.2 months (range 0.1-266.7 months). Pre- and postoperative KPSS scores were 70% (IQR 60-80%). Manifestation of malignant lymphomas in the spine is rare. Similar to the approach taken for spine metastases, a surgical intervention in cases of neurological impairment or manifest or potential instability is indicated, followed by chemoimmunotherapy and radiotherapy.


Assuntos
Linfoma , Vértebras Torácicas , Feminino , Humanos , Vértebras Lombares , Linfoma/diagnóstico , Linfoma/terapia , Masculino , Estudos Retrospectivos , Resultado do Tratamento
7.
Medicine (Baltimore) ; 100(39): e27061, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596109

RESUMO

ABSTRACT: Synchronous double primary malignancies of lymphoma and thyroid cancer are rare. In this retrospective study, we investigated the pathology, clinical characteristics, and treatment outcomes of patients with synchronous lymphoma and thyroid cancer.Of the 1156 newly diagnosed lymphoma patients treated in our hospital between January 1, 2016 and February 1, 2021, 8 cases had lymphoma complicated with thyroid cancer. The clinical data and treatment strategies of 8 cases with synchronous lymphoma and thyroid cancer were retrospectively analyzed.The median age of patients was 56 (25-64) years. All the 8 patients were female and papillary thyroid cancer. Only 1 patient had peripheral T-cell lymphoma, and the other 7 were B-cell lymphoma. Seven of 8 patients had normal free triiodothyronine and free thyroxine at the time of diagnosis. Seven thyroid cancer patients received total thyroidectomy and levothyroxine and the remaining 1 patient has a plan for surgery. At the last follow-up, 7 patients with B-cell lymphoma are alive; the patient with peripheral T-cell lymphoma complicated with thyroid cancer died due to lymphoma progression.Synchronous lymphoma and thyroid cancer are more predominant in women. Histologically, B-cell lymphomas and papillary thyroid cancer subtypes are more common. Attention should be paid to the presence of thyroid nodules in the diagnosis of lymphoma. Biopsy or ultrasound-guided fine needle aspiration of the suspicious thyroid nodule should be performed to exclude thyroid malignancy.


Assuntos
Linfoma/diagnóstico , Linfoma/terapia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/terapia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638774

RESUMO

Targeted immunotherapies have greatly changed treatment of patients with B cell malignancies. To further enhance immunotherapies, research increasingly focuses on the tumor microenvironment (TME), which differs considerably by organ site. However, immunocompetent mouse models of disease to study immunotherapies targeting human molecules within organ-specific TME are surprisingly rare. We developed a myc-driven, primary murine lymphoma model expressing a human-mouse chimeric CD22 (h/mCD22). Stable engraftment of three distinct h/mCD22+ lymphoma was established after subcutaneous and systemic injection. However, only systemic lymphoma showed immune infiltration that reflected human disease. In this model, myeloid cells supported lymphoma growth and showed a phenotype of myeloid-derived suppressor cells. The human CD22-targeted immunotoxin Moxetumomab was highly active against h/mCD22+ lymphoma and similarly reduced infiltration of bone marrow and spleen of all three models up to 90-fold while efficacy against lymphoma in lymph nodes varied substantially, highlighting relevance of organ-specific TME. As in human aggressive lymphoma, anti-PD-L1 as monotherapy was not efficient. However, anti-PD-L1 enhanced efficacy of Moxetumomab suggesting potential for future clinical application. The novel model system of h/mCD22+ lymphoma provides a unique platform to test targeted immunotherapies and may be amenable for other human B cell targets such as CD19 and CD20.


Assuntos
Imunoterapia , Linfoma , Proteínas de Neoplasias , Neoplasias Experimentais , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico , Microambiente Tumoral , Animais , Humanos , Linfoma/genética , Linfoma/imunologia , Linfoma/terapia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Camundongos Transgênicos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Neoplasias Experimentais/genética , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/terapia , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
9.
Br J Radiol ; 94(1127): 20210609, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520671

RESUMO

The use of 18F-FDG PET CT has become an essential part of the management of patients with lymphoma. The last decade has seen unrivalled progress in research efforts to personalise treatment approaches using PET as a predictive imaging biomarker. Critical to this success has been the standardisation of PET methods and reporting, including the 5-point Deauville scale, which has enabled the delivery of robust clinical trial data to develop response-adapted treatment approaches.(1, 2) The utility of PET as a predictive imaging biomarker in assessing treatment success or failure has been investigated extensively in malignant lymphomas. Considerable progress has been made over the last decade, in using PET to direct more personalised "risk-adapted" approaches, as well as an increased understanding of some of the limitations. Arguably the greatest success has been in Hodgkin Lymphoma (HL) where PET was initially demonstrated to be a powerful predictive biomarker (3) and is now routinely used in both early-stage and advanced HL to reduce or escalate the use of chemotherapy as well as guiding the delivery of more selective radiotherapy to patients.


Assuntos
Linfoma/diagnóstico por imagem , Linfoma/terapia , Tomografia por Emissão de Pósitrons/métodos , Medicina de Precisão/métodos , Radiografia Intervencionista/métodos , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Resultado do Tratamento
10.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445701

RESUMO

Chimeric antigen receptor (CAR) T-cells (CAR T-cells) are a promising therapeutic approach in treating hematological malignancies. CAR T-cells represent engineered autologous T-cells, expressing a synthetic CAR, targeting tumor-associated antigens (TAAs) independent of major histocompatibility complex (MHC) presentation. The most common target is CD19 on B-cells, predominantly used for the treatment of lymphoma and acute lymphocytic leukemia (ALL), leading to approval of five different CAR T-cell therapies for clinical application. Despite encouraging clinical results, treatment of other hematological malignancies such as acute myeloid leukemia (AML) remains difficult. In this review, we focus especially on CAR T-cell application in different hematological malignancies as well as strategies for overcoming CAR T-cell dysfunction and increasing their efficacy.


Assuntos
Neoplasias Hematológicas/terapia , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/tendências , Antígenos de Neoplasias/imunologia , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Imunoterapia/métodos , Leucemia/imunologia , Leucemia/terapia , Linfoma/imunologia , Linfoma/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia
11.
Bone Joint J ; 103-B(8): 1400-1404, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34334046

RESUMO

AIMS: The aim of this study was to determine whether there is an increased prevalence of scoliosis in patients who have suffered from a haematopoietic malignancy in childhood. METHODS: Patients with a history of lymphoma or leukaemia with a current age between 12 and 25 years were identified from the regional paediatric oncology database. The medical records and radiological findings were reviewed, and any spinal deformity identified. The treatment of the malignancy and the spinal deformity, if any, was noted. RESULTS: From a cohort of 346 patients, 19 (5.5%) had radiological evidence of scoliosis, defined as a Cobb angle of > 10°. A total of five patients (1.4% of the total cohort) had a Cobb angle of > 40°, all of whom had corrective surgery. No patient with scoliosis had other pathology as a possible cause of the scoliosis and all had been treated with high doses of steroids for leukaemia, either acute or chronic myeloid, or acute lymphoblastic. CONCLUSION: There is an increased prevalence of idiopathic-like scoliosis and larger curves (Cobb angle of > 40°) associated with childhood leukaemia, which has not been previously reported in the literature. Causative factors may relate to the underlying disease process and/or its treatment. Cite this article: Bone Joint J 2021;103-B(8):1400-1404.


Assuntos
Leucemia , Linfoma , Escoliose/epidemiologia , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Leucemia/terapia , Linfoma/terapia , Masculino , Prevalência , Adulto Jovem
12.
Transplant Cell Ther ; 27(10): 863.e1-863.e5, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34293518

RESUMO

Secondary central nervous system (CNS) lymphoma is a rare and often fatal complication of non-Hodgkin lymphoma (NHL). Treatment options include radiation therapy, high-dose systemic chemotherapy, intrathecal chemotherapy, and high-dose chemotherapy with autologous stem cell rescue, but outcomes remain poor. Allogeneic blood or marrow transplantation (alloBMT) is widely used in patients with relapsed/refractory systemic NHL. We sought to understand whether a graft-versus-lymphoma effect could maintain remission in CNS disease. We reviewed outcomes in 20 consecutive patients with secondary CNS lymphoma who underwent alloBMT with nonmyeloablative conditioning using fludarabine, cyclophosphamide, and 200 cGy total body irradiation. For graft-versus-host disease prophylaxis, all patients received post-transplantation cyclophosphamide, mycophenolate mofetil, and a calcineurin inhibitor. With a median follow up of 4.1 years, the median overall survival for the entire cohort was not reached. Median progression-free survival was 3.8 years (95% confidence interval [CI], 5.3 months to not reached). The cumulative incidence of relapse was 25% (95% CI, 5% to 45%), and nonrelapse mortality was 30% (95% CI, 5% to 54%) at 4 years. Of the 5 patients who relapsed, 2 were CNS only, 1 was systemic only, and 2 were combined CNS/systemic. The use of alloBMT in CNS lymphoma merits further investigation.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma , Medula Óssea , Sistema Nervoso Central , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Linfoma/terapia , Recidiva Local de Neoplasia
13.
Oncol Res Treat ; 44(7-8): 375-381, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34289466

RESUMO

BACKGROUND: Aggressive non-Hodgkin lymphomas with secondary central nervous system (CNS) involvement bear a dismal prognosis. Optimal treatment remains so far unclear, and effective treatment options remain an unmet clinical need. Remission rates are in general low, resulting in rapid relapses and palliative care in the majority of patients. High-intensity treatment combining effective CNS-directed chemoimmunotherapy with autologous stem cell transplantation was shown in a recent phase 2 trial to induce durable remissions. Here, we report the outcome of the first real-world patient cohort treated according to the published protocol. METHODS: We retrospectively identified 17 HIV-negative lymphoma patients with secondary CNS involvement, either at first diagnosis or at relapse of lymphoma, treated according to the study protocol published by Ferreri et al. [J Clin Oncol. 2015] at two university medical centers in Germany. Treatment consisted of four cycles of chemoimmunotherapy with a consolidating autologous stem cell transplantation. Adverse events and overall outcome were assessed. RESULTS: Five patients had CNS involvement at first diagnosis and 12 patients at relapse of lymphoma. A complete response was achieved in 9 patients. Median survival was 11 months. Five patients died of septic complications and 4 patients succumbed to progression or relapse of disease. CONCLUSIONS: The outcome of our real-world cohort emphasizes the possible toxic character of the treatment protocol by Ferreri et al. [J Clin Oncol. 2015]. Further improvement in treatment regimens is still an unmet need.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Alemanha , Humanos , Imunoterapia , Linfoma/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
15.
Zhonghua Zhong Liu Za Zhi ; 43(7): 707-735, 2021 Jul 23.
Artigo em Chinês | MEDLINE | ID: mdl-34289565

RESUMO

Lymphoma is one of the most common malignancies in China. In China, there were 6 829 new Hodgkin lymphoma cases and 2 807 deaths in 2020, with 92 834 new non-Hodgkin lymphoma cases and 54 351 deaths. Due to the complicated pathological subtypes and heterogeity, the treatment strategies for lymphoma vary largely. In recent years, with the deep understanding for the nature of lymphoma, much research progress has been achieved in the diagnosis and treatment, leading to a remarkable improvement in survival outcome of patients. In order to update the progress in the treatment of lymphoma worldwide timely, and further improve the level of standardized diagnosis and treatment of lymphoma in China, the China Anti-cancer Association Lymphoma Committee, Chinese Association for Clinical Oncologists, and Medical Oncology Branch of Chinese International Exchange and Promotion Association for Medical and Healthcare organized experts to formulate "Clinical practice guideline for lympoma in China (2021 Edition)" .


Assuntos
Doença de Hodgkin , Linfoma não Hodgkin , Linfoma , China/epidemiologia , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Humanos , Linfoma/diagnóstico , Linfoma/terapia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Oncologia
18.
Nat Med ; 27(8): 1458-1470, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34140705

RESUMO

Gene therapy (GT) has rapidly attracted renewed interest as a treatment for otherwise incurable diseases, with several GT products already on the market and many more entering clinical testing for selected indications. Clonal tracking techniques based on vector integration enable monitoring of the fate of engineered cells in the blood of patients receiving GT and allow assessment of the safety and efficacy of these procedures. However, owing to the limited number of cells that can be tested and the impracticality of studying cells residing in peripheral organs without performing invasive biopsies, this approach provides only a partial snapshot of the clonal repertoire and dynamics of genetically modified cells and reduces the predictive power as a safety readout. In this study, we developed liquid biopsy integration site sequencing, or LiBIS-seq, a polymerase chain reaction technique optimized to quantitatively retrieve vector integration sites from cell-free DNA released into the bloodstream by dying cells residing in several tissues. This approach enabled longitudinal monitoring of in vivo liver-directed GT and clonal tracking in patients receiving hematopoietic stem cell GT, improving our understanding of the clonal composition and turnover of genetically modified cells in solid tissues and, in contrast to conventional analyses based only on circulating blood cells, enabling earlier detection of vector-marked clones that are aberrantly expanding in peripheral tissues.


Assuntos
Ácidos Nucleicos Livres/genética , Vetores Genéticos/genética , Ácidos Nucleicos Livres/efeitos adversos , Terapia Genética , Humanos , Leucemia/genética , Leucemia/terapia , Leucodistrofia Metacromática/genética , Leucodistrofia Metacromática/terapia , Linfoma/genética , Linfoma/terapia
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