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Hiroyuki Shimada

Publications and source records attributed to Hiroyuki Shimada.

At least 37 records · Page 2Linked to original sources
PubMed2005

Endothelial apoptosis induced by inhibition of integrins alphavbeta3 and alphavbeta5 involves ceramide metabolic pathways.

Matrix ligation of integrins alphavbeta3/alphavbeta5 is critical for endothelial survival and angiogenesis. We have previously shown that ceramide, a proapoptotic lipid second messenger, increases during endothelial anoikis (detachment-induced apoptosis). We now show that RGDfV, an integrin alphavbeta3/alphavbeta5 cyclic function-blocking peptide, increased ceramide and decreased sphingomyelin in human brain microvascular endothelial cells (HBMECs) plated on vitronectin, suggesting that sphingomyelin hydrolysis contributes to RGDfV-induced ceramide increase. Desipramine and imipramine, inhibitors of acid sphingomyelinase (ASMase), suppressed RGDfV-induced ceramide increase. Importantly, desipramine, imipramine, and a third ASMase inhibitor, SR33557, but not inhibitors of neutral sphingomyelinase, suppressed RGDfV-induced apoptosis, suggesting that ASMase was required for integrin-mediated apoptosis. Myriocin, an inhibitor of de novo ceramide synthesis, had no effect on RGDfV-induced HBMEC apoptosis. Interestingly, ASMase inhibitors also suppressed the RGDfV-induced loss of spreading on vitronectin. RGDfV induced a similar increase in ceramide and apoptosis in HBMECs on poly-l-lysine or vitronectin, although cells detached only from vitronectin, indicating that cell detachment was not required for RGDfV-induced apoptosis. Our results suggest involvement of ASMase and ceramide in endothelial apoptosis induced by inhibition of integrins alphavbeta3/alphavbeta5, and propose a novel molecular mechanism for the antiangiogenic effect of RGDfV.

Angiogenesis Inhibitors↗
PubMed2005

Enlarged and prominent nucleoli may be indicative of MYCN amplification: a study of neuroblastoma (Schwannian stroma-poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index.

BACKGROUND: According to the International Neuroblastoma Pathology Classification, neuroblastomas exhibiting MYCN amplification (A-MYCN) have unique histologic features-namely, undifferentiated/poorly differentiated subtype with a high mitosis-karyorrhexis index (U/PD-H). Nonetheless, certain tumors possessing these histologic characteristics contain a nonamplified MYCN gene (NA-MYCN). METHODS: The clinical characteristics of patients from the Children's Cancer Group (CCG) 3881 and 3891 studies who had neuroblastoma, U/PD-H, exhibiting A-MYCN (n=68) or NA-MYCN (n=33) were investigated. The histologic and cytologic features of tumors (A-MYCN, n=62; NA-MYCN, n=28) filed at the Pathology Reference Laboratory, Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, were reviewed, and nucleolar areas in undifferentiated neuroblastic cells were evaluated using image analysis methods. RESULTS: All 68 patients whose tumors exhibited A-MYCN had disease that was in an advanced clinical stage (Stage III or IV); 89.7% of these patients were diagnosed between ages 0.5 and 3.5 years, and 67 of the 68 had been treated with the high-risk protocol in the CCG-3891 study. Children whose tumors exhibited NA-MYCN were evenly distributed across all age groups; 30 of these 33 children had advanced-stage disease, and 26 had been treated with a high-risk protocol. The prognosis associated with A-MYCN (event free survival [EFS], 15.7%; overall survival [OS], 22.2%) was significantly poorer than the prognosis associated with NA-MYCN (EFS, 56.1%; OS, 69.3%). The lone histologic/cytologic difference between tumors exhibiting A-MYCN and tumors exhibiting NA-MYCN involved nucleolar appearance. Neuroblastic cells in tumors exhibiting A-MYCN were characterized by the presence of 1 or more large, prominent nucleoli, and the mean nucleolar area was significantly greater in the 18 tumors exhibiting A-MYCN that were assessed (7.63 microm2) than in the 16 tumors exhibiting NA-MYCN that were assessed (5.53 microm2; P=0.004). CONCLUSIONS: Neuroblastomas, U/PD-H, were found to vary in terms of molecular background and clinical behavior. The results of the current study indicate that nucleolar enlargement in neuroblastic cells may be a sign of MYCN amplification.

Biomarkers, Tumor↗
PubMed2005

Neonatal gene therapy of MPS I mice by intravenous injection of a lentiviral vector.

Mucopolysaccharidosis type I (MPS I) is a lysosomal glycosaminoglycan (GAG) storage disorder caused by deficiency of alpha-l-iduronidase (IDUA). In this study, we evaluated the potential to perform gene therapy for MPS I by direct in vivo injection of a lentiviral vector, using an IDUA gene knockout murine model. We compared the efficacy in newborn versus young adult MPS I mice of a single intravenous injection of the lentiviral vector. The extent of transduction was dose-dependent, with the liver receiving the highest level of vector, but other somatic organs reaching almost the same level. The phenotypic manifestations of disease were partially improved in the mice treated as young adults, but were nearly normalized at every end-point measured in the mice treated as neonates. In the neonatally treated mice, the expressed IDUA activity resulted in decreased GAG storage, prevention of skeletal abnormalities, a more normal gross appearance, and improved survival. Most strikingly, significant levels of IDUA enzyme were produced in the brain of mice treated as neonates, with transduction of neurons at high levels. The sustained expression of enzymatically active IDUA in multiple organs had a significant beneficial effect on the phenotypic abnormalities of MPS I, which may be translated to clinical gene therapy of patients with Hurler disease.

Aging↗
PubMed2005

Assessment of NMYC amplification: a comparison of FISH, quantitative PCR monoplexing and traditional blotting methods used with formalin-fixed, paraffin-embedded neuroblastomas.

OBJECTIVE: To determine the degree of agreement between fluorescence in situ hybridization (FISH), Southern blot analysis and LightCycler monoplex polymerase chain reaction (PCR) analysis in the assessment of NMYC gene amplification status in neuroblastoma. STUDY DESIGN: We performed a retrospective analysis of NMYC amplification, using FISH, LightCycler monoplex PCR and Southern blot techniques to assess NMYC amplification in a series of 18 neuroblastomas and 20 histologically normal tissues (15 lymph nodes, 2 pancreas specimens, 1 section each of thyroid, prostate and uterus). RESULTS: Nine neuroblastomas were NMYC amplified, and the remaining cases were nonamplified. All cases yielded interpretable results by Southern blotting and PCR monoplexing techniques. A single case of neuroblastoma was difficult to interpret by FISH due to high background debris. A single case demonstrated low-level NMYC amplification by LightCycler PCR monoplexing but was nonamplified by the other 2 techniques. FISH analysis in 1 case showed amplification, while the other 2 techniques demonstrated nonamplified status. The case in which FISH analysis incorrectly demonstrated amplification was the same one in which there was high background debris. The Southern blot results were reported as amplified or nonamplified, while numeric amplification ratios were obtained by both FISH and PCR LightCycler monoplex analysis. Comparison of these techniques demonstrated FISH to underestimate the degree of amplification in cases in which the amplification level was high by PCR. In fact, FISH appeared to saturate at amplification ratios > 10. CONCLUSION: The study revealed a high level of concordance between the 3 techniques for assessment of NMYC amplification status. However, FISH analysis has the advantage of allowing concurrent assessment of NMYC amplification status and architecture. LightCycler PCR monoplexing appears to have the advantage of more accurately quantitating high levels of NMYC amplification, including those amplified 20-fold or higher. Both FISH and PCR LightCycler monoplexing have the advantage of being performable on formalin-fixed, paraffin-embedded tissue.

Blotting, Southern↗
PubMed2005

[Preoperative factors for postoperative resolution of metamorphopsia in idiopathic macular hole surgery].

PURPOSE: To elucidate factors for resolution of metamorphopsia after successful surgery for idiopathic macular hole. PATIENTS AND METHODS: A series of 15 cases of 15 patients with successful surgery for idiopathic macular hole were evaluated for signs of metamorphopsia before and one year after surgery. Preoperative and postoperative assessments included testing of metamorphopsia using M-CHART and optical coherence tomography. The postoperative state of the metamorphopsia was judged to have resolved when the test score was 0.2 or less and to be residual when it was more than 0.2. Classification of preoperative factors in two groups of patients included evaluation of metamorphopsia score, visual acuity, optical coherence tomography findings, and clinical stage of macular hole. RESULTS: Six of 15 eyes (40%) showed postoperative resolution of metamorphopsia. There was no significant correlation of postoperative metamorphopsia score with preoperative score or preoperative visual acuity. Eyes with postoperative resolution of metamorphopsia had a macular hole with a significantly smaller diameter and a significantly thinner retina surrounding the hole. Two eyes with clinical stage 4 macular hole had residual metamorphopsia after surgery. CONCLUSIONS: The diameter of a macular hole and the thickness of the retina surrounding a macular hole are significant preoperative factors for postoperative resolution of metamorphopsia after idiopathic macular hole surgery.

Aged↗
PubMed2005

[Chronic GVHD with polymyositis after non-myeloablative stem cell transplantation].

A 57-year-old man underwent an autologous hematopoietic stem cell transplant for mantle cell lymphoma in August 1999. Anemia and thrombocytopenia appeared in November 2001. He was diagnosed with further hematological examination as having acute myeloid leukemia with multilineage dysplasia following secondary myelodysplastic syndrome. He received the allogeneic hematopoietic stem cell transplant from his HLA DRB1 locus mismatched brother in May 2002. The nonmyeloablative preparative regimen consisted of fludarabine 30mg/m2 for 6 days and busulfan 4mg/kg for 2 days. Eosinophilia, decrease of lacrimal fluid and liver dysfunction appeared on Day 104. We diagnosed this as chronic GVHD and treated the patient with prednisolone 10 mg/day. Thereafter, his chronic GVHD gradually improved. He had fever and myalgia in the extremities and lumbar region with elevated serum CPK and aldolase in January 2003. Histological examination led to a diagnosis of polymyositis simultaneously with chronic GVHD. Prednisolone 50 mg/day as an initial dose was started for the polymyositis following which the prednisolone dose was gradually tapered off. The polymyositis improved promptly after the administration of prednisolone and remains in remission with a current maintenance program of prednisolone 5 mg/day.

Chronic Disease↗
PubMed2004

Surgical excision of neovascularization in retinal angiomatous proliferation.

BACKGROUND: We report the postoperative outcomes of surgical neovascularization excision in patients with retinal angiomatous proliferation (RAP). METHODS: Nine eyes of eight patients with RAP who underwent surgical excision of neovascularization were studied. Surgical indications were as follows: RAP diagnosed by fluorescein and indocyanine green angiography, foveal or perifoveal neovascularization, preoperative visual acuity of 0.1 or less, Yannuzzi's stage II with detachment of retinal pigment epithelium (RPE) or stage III, and leakage on late-phase fluorescein angiography. After cataract surgery, vitreous surgery and neovascularization excision were conducted, followed by fluid-air or fluid-gas exchange. RESULTS: Visual acuity was 0.02-0.1 before surgery and 0.03-0.2 after surgery. Macular hole formation was seen in one eye but did not lead to retinal detachment. In two eyes, subretinal bleeding occurred during excision leading to vitreous bleeding after surgery. Although defects of the RPE and choriocapillaries were observed after surgery, the exudation and bleeding were absorbed. CONCLUSIONS: In stage II RAP cases with RPE detachment, surgical excision maintains constant postoperative visual acuity but results in defects of RPE and choriocapillaris; therefore, other treatment options should be examined. Surgical excision of stage III RAP seems to be promising, as postoperative visual acuity remains stable after neovascularization removal in those advanced pathologic situations.

Aged↗
PubMed2004

TrkA expression in peripheral neuroblastic tumors: prognostic significance and biological relevance.

BACKGROUND: This study was conducted to investigate the prognostic significance and biologic relevance of trkA expression levels in peripheral neuroblastic tumors (pNTs) (i.e., neuroblastoma, ganglioneuroblastoma, and ganglioneuroma). METHODS: Levels of trkA expression from a total of 265 pNTs were determined by quantitative polymerase chain reaction analysis with Genescan software. The results were analyzed according to histopathology (favorable histology [FH] vs. unfavorable histology [UH] according to the International Neuroblastoma Pathology Classification) and MYCN tumor status (amplified vs. nonamplified) along with clinical stage and outcomes of the patients. RESULTS: The levels of trkA expression differed significantly between the group of patients who were alive and well (n = 170 patients) and the group that had progressed or died (n = 95 patients) and between the group that was alive (n = 188 patients) and the group that died (n = 77 patients). However, the trkA expression levels were not independent predictors of clinical outcome when the proportional hazards model contained the known prognostic variables of clinical stage, histopathology, and MYCN status (all tests were done in 196 patients). In the neuroblastoma category (n = 173 tumors), tumors in the FH/nonamplified MYCN subset (n = 112 tumors) expressed higher levels of trkA and showed an age-dependent neuroblastic differentiation: They were classified into either a poorly differentiated subtype (n = 91 tumors; all patients age < 1.5 years at diagnosis) or a differentiating subtype (n = 21 tumors; 57% of patients ages 1.5-5.0 years). Tumors in the UH/amplified MYCN subset (n = 30 tumors) expressed significantly lower levels of trkA and showed very limited neuroblastic differentiation. Tumors in the FH/amplified MYCN subset were very rare (n = 3 tumors) and expressed higher levels of trkA. Tumors in the UH/nonamplified MYCN subset (n = 28 tumors) had trkA levels in a wide range and showed limited neuroblastic differentiation. CONCLUSIONS: For patients with pNTs, levels of trkA expression did not add significant information to prognostic grouping, as defined by the combination of clinical stage, histopathology, and MYCN status. There was a biologically relevant correlation between molecular properties (trkA expression and MYCN status) and histopathologic features of the tumors in the neuroblastoma category.

Biomarkers, Tumor↗
PubMed2004

First case of aplastic anemia in a Japanese child with a homozygous missense mutation in the NBS1 gene (I171V) associated with genomic instability.

The NBS1 gene is strongly linked to several factors involved in genome integrity. Functional disruption of NBS1 could therefore induce genomic instability and carcinogenesis. Four children with acute lymphoblastic leukemia have been reported to be heterozygous for a germline and/or somatic missense mutation in NBS1, leading to the I171V substitution. We screened healthy controls and pediatric patients with hematological malignancies and aplastic anemia (AA) for the presence of I171V. Of the 62 patients, one individual with AA was confirmed to harbor a homozygous I171V mutation. Genetic analysis of NBS1 in this patient and her healthy parents indicated that she inherited the germline I171V mutation from her father and the wild-type allele from her mother, and that the second I171V hit occurred on the wild-type allele early in embryonic development. Furthermore, cytogenetic analysis of lymphoblastic cell lines from the patient indicated a remarkable increase in numerical and structural chromosomal aberrations in the absence of clastogens, suggesting that she potentially carried genomic instability. This is the first report of AA with a homozygous I171V mutation. We hypothesize that NBS1 may play an important role in the pathogenesis of AA.

Anemia, Aplastic↗
PubMed2004

The matrix metalloproteinase inhibitor prinomastat enhances photodynamic therapy responsiveness in a mouse tumor model.

Photodynamic therapy (PDT) clinical results are promising; however, tumor recurrences can occur and, therefore, methods for improving treatment efficacy are needed. PDT elicits direct tumor cell death and microvascular injury as well as expression of angiogenic, inflammatory, and prosurvival molecules. Preclinical studies combining antiangiogenic drugs or cyclooxygenase-2 inhibitors with PDT show improved treatment responsiveness (A. Ferrario et al., Cancer Res 2000;60:4066-9; A. Ferrario et al., Cancer Res 2002;62:3956-61). In the present study, we evaluated the role of Photofrin-mediated PDT in eliciting expression of matrix metalloproteinases (MMPs) and modulators of MMP activity. We also examined the efficacy of a synthetic MMP inhibitor, Prinomastat, to enhance tumoricidal activity after PDT, using a mouse mammary tumor model. Immunoblot analysis of extracts from PDT-treated tumors demonstrated strong expression of MMPs and extracellular MMP inducer along with a concomitant decrease in expression of tissue inhibitor of metalloproteinase-1. Gelatin zymography and enzyme activity assays performed on protein extracts from treated tumors confirmed the induction of both latent and enzymatically active forms of MMP-9. Immunohistochemical analysis indicated that infiltrating inflammatory cells and endothelial cells were primary sources of MMP-9 expression after PDT, whereas negligible expression was observed in tumor cells. Administration of Prinomastat significantly improved PDT-mediated tumor response (P = 0.02) without affecting normal skin photosensitization. Our results indicate that PDT induces MMPs and that the adjunctive use of an MMP inhibitor can improve PDT tumor responsiveness.

Animals↗
PubMed2004

Stromal matrix metalloproteinase-9 regulates the vascular architecture in neuroblastoma by promoting pericyte recruitment.

Advanced stages of neuroblastoma show increased expression of matrix metalloproteinases MMP-2 and MMP-9, that have been implicated in many steps of tumor progression, suggesting that they play a contributory role. Using pharmacological and genetic approaches, we have examined the role of these MMPs in progression of SK-N-BE (2).10 human neuroblastoma tumors orthotopically xenotransplanted into immunodeficient mice. Mice treated with Prinomastat, a synthetic inhibitor of MMPs, showed an inhibition of tumor cell proliferation in implanted tumors and a prolonged survival (50 versus 39 days in control group, P < 0.035). Treatment with Prinomastat did not affect formation of liver metastases (P = 0.52) but inhibited intravascular colonization by the tumor cells in the lung by 73.8% (P = 0.03) and angiogenesis in both primary tumors and experimental liver metastases. The primary tumors from Prinomastat-treated mice showed a 39.3% reduction in endothelial area detected by PECAM/CD31 staining in tumor sections (P < 0.001), primarily due to the presence of smaller vessels (P = 0.004). MMP-2 is expressed by neuroblastoma tumor cells and stromal cells, whereas MMP-9 is exclusively expressed by stromal cells, particularly vascular cells. To examine the contribution of MMP-9 to tumor angiogenesis, we generated RAG1/MMP-9 double-deficient mice. We observed a significant inhibition of angiogenesis in the immunodeficient RAG1/MMP-9 double-deficient mice orthotopically implanted with tumor cells (P = 0.043) or implanted s.c. with a mixture of tumor cells and Matrigel (P < 0.001). Using an FITC-labeled lectin, we demonstrated an inhibition in the architecture of the tumor vasculature in MMP-9-deficient mice, resulting in fewer and smaller blood vessels. These changes were associated with a 48% decrease in pericytes present along microvessels. Taken together, the data demonstrate that in neuroblastoma, stromally derived MMP-9 contributes to angiogenesis by promoting blood vessel morphogenesis and pericyte recruitment.

Cell Division↗
PubMed2004

Large cell neuroblastoma: a distinct phenotype of neuroblastoma with aggressive clinical behavior.

BACKGROUND: Among cases of undifferentiated and poorly differentiated tumors in the neuroblastoma (Schwannian stroma-poor) category, the authors histologically identified a group of rare tumors, known as large cell neuroblastomas (LCNs), that are composed of large cells with sharply outlined nuclear membranes and 1-4 prominent nucleoli. METHODS: Histologic and immunohistochemical features of LCN were characterized. Morphologic characteristics, clinical features, and MYCN status were compared between LCNs and conventional neuroblastomas documented in the files of two European centers (the Sir James Spence Institute of Child Health, Royal Victoria Infirmary, University of Newcastle, Newcastle upon Tyne, United Kingdom, and the Medical and Health Sciences Center, University of Pécs, Pécs, Hungary). RESULTS: Of 92 peripheral neuroblastic tumors (pNTs; including neuroblastoma [n = 81]; ganglioneuroblastoma, intermixed [n = 6]; and ganglioneuroblastoma, nodular [n = 5]), 7 (7.6%) qualified as LCN. All 7 LCNs were classified as having unfavorable histology (UH) according to the International Neuroblastoma Pathology Classification. The LCNs were composed of monomorphous undifferentiated neuroblasts and shared certain histologic features, such as a high incidence of high mitosis-karyorrhexis index and a low incidence of calcification, with other neuroblastomas in the conventional UH (c-UH) group. These features were significantly different from those of neuroblastomas in the conventional favorable histology (c-FH) group. On immunohistochemical analysis, LCN tumor cells were positive for neuron-specific enolase (5 of 5 cases), protein gene product 9.5 (5 of 5 cases), synaptophysin (5 of 5 cases), tyrosine hydroxylase (focally in 3 of 3 cases), and NB84 (3 of 5 cases) and negative for CD99. Patients with LCN and patients with c-UH disease had similar clinical features (diagnosis at age > 1 year, often with distant metastasis). The clinical features of these patients also were significantly different from those of patients with c-FH disease. Further analysis demonstrated that the LCN group was significantly different from both the c-UH and c-FH groups with respect to MYCN status (MYCN amplification, 4 of 5 vs. 3 of 17 vs. 8 of 17, respectively; P = 0.023) and survival rate (4-year expected survival, 0% vs. 71% vs. 17%, respectively; P < 0.01). CONCLUSIONS: Because of its unique clinicopathologic features, the authors propose that LCN be recognized as a distinct entity within the undifferentiated and poorly differentiated subtypes of the neuroblastoma category.

Child↗
PubMed2004

A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis.

BACKGROUND: Early-onset familial Alzheimer disease is caused by mutations in the amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes. Phenotypic diversity has been reported to be associated with various mutations in PSEN1. Various mutations of PSEN1 have been reported in cases of early-onset Alzheimer disease with spastic paraparesis. OBJECTIVE: To describe a novel mutation in the PSEN1 gene associated with early-onset Alzheimer disease with spastic paraparesis. PATIENT AND METHODS: The patient was a 27-year-old man who developed early-onset dementia with spastic paraparesis. We examined sequences of the PSEN1, PSEN2, and APP genes from the patient and his family. To detect a possible mutation effect on the production of amyloid-beta peptide (Abeta), transfected HEK293 cells were examined for Abeta42 and Abeta40 production. RESULTS: We found a novel mutation (Leu85Pro) in PSEN1. This mutation influenced the production of Abeta, resulting in a 2-fold elevation of Abeta42 production and of the Abeta42/40 ratio. CONCLUSION: To our knowledge, this is the first report of very early-onset Alzheimer disease with spastic paraparesis and with the visual variant form of the disease, which is associated with visuospatial cognitive disorder. The Leu85Pro mutation in PSEN1 was pathogenic.

Adult↗
PubMed2004

Neuroblastoma in an adult.

Neuroblastoma is extremely rare in adults. Advances in classification and therapy have been recently made by an analysis of pediatric tumors. We present the case of a 39-year-old man who had Stage 1 neuroblastoma with unfavorable histologic features that was treated with surgery only. Neuroblastoma should be considered as a diagnosis for adult patients with a suprarenal mass and, if confirmed, neuroblastoma in adults should be classified and treated according to pediatric guidelines.

Adrenal Gland Neoplasms↗
PubMed2004

Pars plana suture fixation for intraocular lenses dislocated into the vitreous cavity using a closed-eye cow-hitch technique.

We describe a modified intraocular cow-hitch technique for pars plana suture fixation of intraocular lenses (IOLs) that dislocated into the vitreous cavity in 3 patients who had a 3-port vitrectomy and IOL implantation because of retinal disease. To reposition the dislocated IOL after the residual vitreous was removed, 2 additional sclerotomies for suture fixation were made 3.0 mm posterior to the limbus. A loop (cow-hitch knot) was made with 10-0 polypropylene for suture fixation. After the neck of the cow-hitch loop was grasped with an intraocular forceps, the loop was used to lasso a haptic of the dislocated IOL, which was then pulled forward to the sclerotomy. The same procedure was used for the other haptic, and both sutures were secured to the sclera under scleral flaps. In all patients, the dislocated IOLs were repositioned without the need for extraction. The procedures were uneventful. Pars plana suture fixation with the intraocular cow-hitch technique can be used to reposition an IOL that has dislocated into the vitreous cavity.

Adult↗
PubMed2004

Epstein-Barr virus-associated posttransplant lymphoproliferative disorder after a cord blood stem cell transplantation presenting with pulmonary nodules.

Sixteen months after a cord blood stem cell transplantation, a 6-year-old girl was diagnosed with Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (EBV-PTLD). A CT scan revealed nodules in both lungs, but the patient had neither lymphadenopathy nor other lesions. The diagnosis was confirmed by histopathologic evaluation and the increased level of EBV DNA in the peripheral blood. The patient was successfully treated with rituximab, and a complete regression of the tumors was achieved. This case reveals the need to include EBV-PTLD in the differential diagnosis of pulmonary nodules, as well as demonstrating that rituximab may be effective treatment of EBV-PTLD after cord blood stem cell transplantation.

Antibodies, Monoclonal↗