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Primary gastrointestinal T/NK cell lymphoma (GI-TNKL) is an uncommon and heterogeneous group of lymphoid malignancies. We aimed to investigate their subtype distribution, clinicopathologic characteristics, and clinical outcomes. A total of 38 GI-TNKL cases and their clinical and pathological characteristics were analyzed. GI-TNKL occurred in adults with a median patient age in the sixth decade of life and showed a slight male predominance. The most common histologic type was extranodal NK/T-cell lymphoma, nasal type (ENKTL; 34.2%), followed by monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL; 31.6%), intestinal T-cell lymphoma, NOS (ITCL, NOS, 18.4%), anaplastic large cell lymphoma, ALK-negative (ALCL, ALK-; 13.2%). The small intestine was the primary affected region. More than 90% of patients complained of various GI symptoms and cases with advanced Lugano stage, high IPI score, or bowel perforation that required emergent operation were not uncommon. GI-TNKL also showed aggressive behavior with short progression-free survival and overall survival. This thorough clinical and pathological descriptive analysis will be helpful for accurate understanding, diagnosis, and treatment.
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BACKGROUND/AIMS: Although the use of surveillance 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is discouraged in patients with diffuse large B-cell lymphoma, its usefulness in different subtypes has not been thoroughly investigated. METHODS: We retrospectively evaluated 157 patients who showed positive results on surveillance FDG-PET/CT every 6 months following complete response for up to 5 years. All of the patients also underwent biopsies. RESULTS: Seventy-eight (49.6%) of 157 patients had true positive results; the remaining 79 (50.3%), including eight (5.1%) with secondary malignancies, were confirmed to yield false positive results. Among the 78 patients with true positive results, the disease in seven (8.9%) had transformed to a different subtype. The positive predictive value (PPV) of FDG-PET/CT for aggressive B-cell non-Hodgkin's lymphoma (NHL) was lower than that for indolent B-cell or aggressive T-cell NHL (p = 0.003 and p = 0.018, respectively), especially in patients with a low/low-intermediate international prognostic index (IPI) upon a positive PET/CT finding. On the other hand, indolent B-cell and aggressive T-cell NHL patients showed PPVs of > 60%, including those with low/low-intermediate secondary IPIs. CONCLUSION: The role of FDG-PET/CT surveillance is limited, and differs according to the lymphoma subtype. FDG-PET/CT may be useful in detecting early relapse in patients with aggressive T-cell NHL, including those with low/low-intermediate risk secondary IPI; as already known, FDG-PET/CT has no role in aggressive B-cell NHL. Repeat biopsy should be performed to discriminate relapse or transformation from false positive findings in patients with positive surveillance FDG-PET/CT results.
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Linfoma no Hodgkin , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Humanos , Linfoma no Hodgkin/diagnóstico por imagen , Recurrencia Local de Neoplasia , Tomografía de Emisión de Positrones , Radiofármacos , Estudios RetrospectivosRESUMEN
Primary effusion lymphoma (PEL) is a B-cell non-Hodgkin's lymphoma that is usually characterized by lymphomatous effusions in the body cavity without any detectable tumor masses. According to the World Health Organization (WHO) schema for tumor classification, PEL is defined by the presence of human herpesvirus 8 (HHV8) in malignant lymphoid cells. However, a subset of effusion-based B-cell lymphoma is not HHV8-positive and exhibits different clinicopathological characteristics. The 2017 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues does not list HHV8-negative effusion-based lymphoma, which remains an underappreciated B-cell lymphoma, as an individual entity. The present study reports a case of this rare type of lymphoma with indolent clinical behavior in a 75-year-old male patient receiving only symptomatic treatment. Additionally, a review of similar cases reported in the English literature is presented.
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PURPOSE: Histiocytic and dendritic cell neoplasms are rare hematologic tumors. This study aimed to describe the epidemiologic features of the entire spectrum of histiocytic and dendritic cell neoplasms, including clinicopathological variables and patient outcomes. MATERIALS AND METHODS: We comprehensively reviewed 274 patients who were diagnosed with histiocytic and dendritic neoplasms at Severance Hospital, Seoul, South Korea between 1995 and 2018. RESULTS: The most common neoplasm was Langerhans cell histiocytosis (LCH), followed by dermal xanthogranuloma. Among non-LCH sarcomas, histiocytic sarcoma (HS) showed a relatively high prevalence, followed by follicular dendritic cell sarcoma (FDCS). Disseminated juvenile xanthogranuloma (DJG), Erdheim-Chester disease (ECD), indeterminate dendritic cell tumor (IDCT), and interdigitating dendritic cell sarcoma (IDCS) rarely occurred. Generally, these tumors presented in childhood, although the non-LCH sarcoma (HS/FDCS/IDCS/IDCT) group of tumors and ECD occurred in late adulthood. Multiorgan involvement and advanced Ann-Arbor stage, as well as recurrence and death of disease, were not uncommon. The non-LCH sarcoma group had the worst overall survival, compared to the DJG, ECD, and LCH groups. CONCLUSION: Our findings indicate that histiocytic and dendritic cell neoplasms exhibit heterogeneous epidemiologic characteristics and that some patients may have unfavorable outcomes, especially those with non-LCH sarcoma.
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Células Dendríticas/patología , Histiocitos/patología , Trastornos Histiocíticos Malignos/patología , Sarcoma Histiocítico/patología , Adulto , Niño , Sarcoma de Células Dendríticas Foliculares/epidemiología , Sarcoma de Células Dendríticas Foliculares/patología , Femenino , Trastornos Histiocíticos Malignos/epidemiología , Sarcoma Histiocítico/epidemiología , Histiocitosis de Células de Langerhans/epidemiología , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Prevalencia , República de Corea/epidemiología , Seúl , Xantogranuloma Juvenil/epidemiología , Xantogranuloma Juvenil/patologíaRESUMEN
Herein, we describe the first case of renal intravascular large B cell lymphoma in Korea occurring in a 66-year-old female. She presented with mild fever and dyspnea. On physical and laboratory evaluations, hemophagocytic lymphohistiocytosis was suspected, but the bone marrow biopsy results were unremarkable. During the work-up, massive proteinuria developed, which led to a renal biopsy. The renal architecture was relatively well-preserved, but the glomeruli were hypercellular with the infiltration of atypical, large lymphoid cells with increased nucleus-cytoplasm ratio and clumped chromatin. Similar cells were also present in the peritubular capillaries. The tumor cells exhibited membranous staining for CD20 and CD79a. After the diagnosis of intravascular large B cell lymphoma, the patient received rituximab-based chemotherapy under close follow-up.
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PURPOSE: Forkhead box C1 (FOXC1) is critical for maintaining bone marrow microenvironments during hematopoiesis, but its role in hematological malignancies remains obscure. Here, we investigated whether FOXC1 regulates tumor dormancy and activation in the microenvironments of T and natural killer (NK) cell lymphomas. MATERIALS AND METHODS: One hundred and twenty cases of T and NK cell lymphomas were included; the immunohistochemical expression of FOXC1 was investigated in stromal cells, and numbers of FOXC1+ stromal cells were counted. Furthermore, the expression of phosphorylated p38 (p-p38) and phosphorylated ERK1/2 (p-ERK1/2) in tumor cells was investigated using immunohistochemistry. RESULTS: FOXC1 was variably expressed in C-X-C motif chemokine 12-associated reticular stromal cells, histiocytes, (myo)fibroblasts, and endothelial cells. The phenotypes of cases were categorized as dormant (high p-p38/low p-ERK1/2; n=30, 25.0%), active (high p-ERK1/2/low p-p38; n=25, 20.8%), or intermediate (others; n=65, 54.2%). Lower FOXC1+ stromal cell infiltration was associated with the dormant phenotype, the precursor T lymphoblastic leukemia/lymphoma subtype, and inferior overall survival rates, whereas higher FOXC1+ stromal cell infiltration was associated with the active phenotype and favorable patient prognosis (p < 0.05 for all). CONCLUSION: These results suggested that FOXC1+ stromal cells within the microenvironments of T and NK cell lymphomas might be related to tumor phenotypes.
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Factores de Transcripción Forkhead/metabolismo , Linfoma de Células T/diagnóstico , Células del Estroma/patología , Microambiente Tumoral , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Factores de Transcripción Forkhead/análisis , Humanos , Inmunohistoquímica , Células Asesinas Naturales/patología , Linfoma de Células T/mortalidad , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Linfocitos T/patología , Análisis de Matrices Tisulares , Adulto JovenRESUMEN
Although MYC and BCL2 co-expression in diffuse large B cell lymphoma (DLBCL) is associated with inferior prognosis, it remains uncertain whether upfront autologous hematopoietic stem cell transplantation (ASCT) is beneficial in this lymphoma. This study aimed to investigate whether ASCT consolidation could have a positive role for patients with MYC and BCL2 co-expression (double-expressor lymphoma, DEL). We retrospectively evaluated 67 DLBCL patients who underwent upfront ASCT following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) were 82.3% and 79.2%, respectively. There were 23 (34.3%) patients with DEL and 51 (76.1%) patients with non-germinal center B cell (GCB) subtype. The 5-year OS and PFS of patients with DEL were not different from those with non-DEL (P = 0.429 and P = 0.614, respectively). No survival difference for OS and PFS was also observed between GCB and non-GCB subtypes (P = 0.950 and P = 0.901, respectively). The OS and PFS were comparable for patients with DEL and non-DEL and both GCB and non-GCB subtypes. In conclusion, MYC and BCL2 co-expression did not have a poor prognostic impact among high-risk patients with DLBCL treated with upfront ASCT regardless of molecular classification. This preliminary study suggested that the role of consolidative ASCT is needed to be evaluated in a prospective randomized clinical trial.
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Regulación Neoplásica de la Expresión Génica , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/terapia , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Estudios Retrospectivos , Factores de Riesgo , Trasplante Autólogo/métodos , Vincristina/uso terapéutico , Adulto JovenRESUMEN
The gastrointestinal (GI) tract is a prevalent site for extranodal lymphomas. Some subtypes of GI tract lymphomas are aggressive and have dismal clinical outcomes. Therefore, prompt histopathologic detection of such types can be very important. We thus introduce a practical approach in the histopathologic diagnosis of GI lymphomas according to the revised World Health Organization (WHO) classification. When lymphocyte proliferation is found in the GI tract, a stepwise approach can help narrow down the differential diagnoses. When considering subtype incidence, macroscopic findings, and microscopic patterns, applying a first-line marker battery of CD20, CD3, CD30, and Epstein-Barr virus-encoded RNAs can effectively narrow down the top differential diagnoses at the initial step. Generally, the most common subtype among GI tract lymphomas is B-cell non-Hodgkin lymphoma identified by CD20 expression, followed by T-cell and NK-cell non-Hodgkin lymphomas identified by the CD3 expression, and some subtypes are defined by Epstein-Barr virus infection or CD30 expression. Macroscopically, lymphomas present as various gross types, such as large masses, small lesions, superficial and shallow lesions, polyp-like or polyposis-like features, or ulcer/necrosis/perforation. Microscopically, large pleomorphic cells or small to medium-sized tumor cells grow with various architectures and tumor microenvironments. Incorporation of macroscopic and microscopic features and the stepwise immunophenotyping may be a practical approach to the differential diagnosis of aggressive lymphoma, indolent/low-grade lymphoma, or benign to indolent lymphoproliferative disease. Exceptions always exist; this approach focuses on the relatively prevalent circumstances of lymphomatous lesions initially encountered in the GI tract.
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Antígenos CD20 , Biomarcadores de Tumor , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/patología , Herpesvirus Humano 4/genética , Antígeno Ki-1 , Linfoma/diagnóstico , Linfoma/patología , Linfocitos B/patología , Neoplasias Gastrointestinales/virología , Humanos , Inmunofenotipificación , Linfoma/virología , ARN Viral , Linfocitos T/patologíaRESUMEN
PURPOSE: The treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expression in previous studies enrolling patients with a wide range of CD30 expression level. Thus, this study explored the efficacy of BV in high-CD30-expressing non-Hodgkin lymphoma (NHL) patients most likely to benefit. MATERIALS AND METHODS: This phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30-expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks. The primary endpoint was > 40% disease control rate, consisting of complete response (CR), partial response (PR), or stable disease. We defined high CD30 expression as ≥ 30% tumor cells positive for CD30 by immunohistochemistry. RESULTS: High-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma. The disease control rate was 48.5% (16/33) including six CR and six PR; six patients (4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survival were not associated with CD30 expression levels. Over a median of 29.2 months of follow-up, the median progression-free and overall survival rates were 1.9 months and 6.1 months, respectively. The most common adverse events were fever (39%), neutropenia (30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a post-hoc analysis for the association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1- negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients (13.3%, 2/15). CONCLUSION: BV performance as a single agent was acceptable in terms of disease control rates and toxicity profiles, especially MUM1-negative patients.
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Antineoplásicos Inmunológicos/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Antígeno Ki-1/metabolismo , Linfoma no Hodgkin/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Resultado del TratamientoRESUMEN
Dysregulated matrix metalloproteinase (MMP) gene expression is a major cause of the degradation of lung tissue that is integral to emphysema pathogenesis. Cigarette smoking (CS) increases MMP gene expression, a major contributor to emphysema development. We previously reported that Zbtb7c is a transcriptional repressor of several Mmp genes (Mmps-8, -10, -13, and -16). Here, we show that Zbtb7c knockout mice have mild emphysema-like phenotypes, including alveolar wall destruction, enlarged alveoli, and upregulated Mmp genes. Alveolar size and Mmp gene expression in Zbtb7c-/- mouse lungs are increased more severely upon exposure to CS, compared to those of Zbtb7c+/+ mouse lungs. These observations suggest that Zbtb7c degradation or absence may contribute to the pathogenesis of emphysema.
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Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Enfisema/genética , Pulmón/patología , Metaloproteinasas de la Matriz/genética , Fenotipo , Factores de Transcripción/deficiencia , Factores de Transcripción/genética , Transcripción Genética/genética , Animales , Fumar Cigarrillos/efectos adversos , Técnicas de Inactivación de Genes , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , RatonesRESUMEN
Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease manifesting with a persistent high-spiking fever, a typical rash, and lymphadenopathy. Endogenous factors related to interleukin-1, such as S100A8/A9 and several chemokines including CXCL10, CXCR3, and CXCL13, potentially play roles in its pathogenesis. We describe the histopathological features and chemokine expression pattern in lymph nodes (LNs) of patients with AOSD. Formalin-fixed, paraffin-embedded excisional LN tissues from 48 patients with AOSD were histologically reviewed. CXCL10, CXCR3, CXCL13, and S100A8/A9 expression was evaluated immunohistochemically. The pathology of LN was characterized by paracortical hyperplasia with proliferation of histiocyte, immunoblast, CD8-positive lymphoid cell and blood vessel. Most cases required differential diagnosis from dermatopathic lymphadenitis (n = 16, 33.3%), T cell lymphoma (n = 11, 22.9%), and histiocytic necrotizing lymphadenitis (HNL) (n = 9, 18.8%). The expression levels of CXCL10 and CXCR3 were higher in patients with AOSD than in those with T cell lymphoma, HNL, tuberculous lymphadenitis, and reactive hyperplasia. It is important to recognize the aforementioned histopathologic findings of nodal involvement of AOSD because improper diagnosis and treatment can be avoided. Immunohistochemical staining for chemokines, CXCL10 and CXCR3, may aid in differentiating AOSD from other mimickers.
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Quimiocinas/metabolismo , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Enfermedad de Still del Adulto/inmunología , Enfermedad de Still del Adulto/patología , Adulto , Calgranulina A/sangre , Calgranulina A/metabolismo , Calgranulina B/sangre , Calgranulina B/metabolismo , Quimiocina CXCL10/sangre , Quimiocina CXCL10/metabolismo , Quimiocina CXCL13/sangre , Quimiocina CXCL13/metabolismo , Quimiocinas/sangre , Diagnóstico Diferencial , Femenino , Linfadenitis Necrotizante Histiocítica/diagnóstico , Humanos , Inmunohistoquímica , Ligandos , Linfadenitis/diagnóstico , Linfoma de Células T/diagnóstico , Masculino , Persona de Mediana Edad , Receptores CXCR3/metabolismo , Estudios Retrospectivos , Enfermedad de Still del Adulto/diagnóstico , Receptor Toll-Like 4/metabolismo , Tuberculosis Ganglionar/diagnósticoAsunto(s)
Biomarcadores de Tumor/genética , Neoplasias Gastrointestinales/genética , Regulación Neoplásica de la Expresión Génica , Células Asesinas Naturales/metabolismo , Linfoma de Células T/genética , Neoplasias Gastrointestinales/patología , Perfilación de la Expresión Génica , Humanos , Células Asesinas Naturales/patología , Linfoma de Células T/patología , PronósticoRESUMEN
BACKGROUND: Stored platelets undergo deleterious changes, referred to as platelet storage lesions (PSLs), which accelerate the desialylation of platelets and result in their phagocytosis and clearance by hepatic macrophages. Recent studies have reported that Ashwell-Morell receptor binds to desialylated platelets, thereby inducing hepatic thrombopoietin (TPO) production in a mouse model. Therefore, this study aimed to demonstrate these relationships between PSL and hepatic TPO production in human study. METHODS: Platelet concentrates (PCs) were obtained from 5 healthy volunteers and the remaining were discarded samples from the blood bank. PCs were divided into two halves, and stored either at 22 or 4 °C. Experiments were conducted using serial samples. Desialylation was assessed using flow cytometry, and structural changes were visualized using electron microscopy. Following co-culture of HepG2 cells (HB-8065, ATCC) with isolated platelets, hepatic TPO production was determined using real-time quantitative polymerase chain reaction and the supernatant TPO level was measured using a Luminex kit. RESULTS: For 5 days of storage duration, platelet counts were not influenced by the storage conditions, but the degree of desialylation was proportional to the storage duration. Significant changes in the platelet surface and structure according to storage conditions were noted in electron microscopy. HepG2 cells incubated with aged platelets expressed more TPO mRNA, and supernatant TPO levels were proportional to the storage duration. Refrigeration also influenced on the results of this study, but they were not statistically significant. CONCLUSIONS: This is the first study to demonstrate that, in vitro, aging and refrigeration affect the integrity of human platelets, resulting in induction of hepatic TPO mRNA and protein expression.
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Plaquetas/metabolismo , Hígado/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Preservación Biológica , Temperatura , Trombopoyetina/biosíntesis , Acetilglucosamina/metabolismo , Adulto , Plaquetas/ultraestructura , Citometría de Flujo , Células Hep G2 , Humanos , Persona de Mediana Edad , Recuento de Plaquetas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Trombopoyetina/genética , Trombopoyetina/metabolismoRESUMEN
Because there are few studies regarding the clinical impact of circulating EBV-DNA in peripheral T-cell lymphomas (PTCLs), we tried to evaluate the role of EBV-DNA in whole blood as a prognostic factor for PTCL. We retrospectively reviewed 110 PTCL patients with median age of 63 (20-94) years. Forty-seven patients (42.7%) showed positive results for EBV-DNA, and these patients also had stage III/IV disease, elevated lactic dehydrogenase, and low albumin level (P = 0.007, P = 0.004, P = 0.002, respectively). The 5-year overall survival (OS) and progression free survival (PFS) were 21.0% and 18.0%. Univariable analysis showed that positive EBV-DNA was related with inferior OS and PFS (P = 0.015 and P < 0.001, respectively). Multivariable analysis showed that poor performance status, extranodal involvement more than one site and positive EBV-DNA results were related with OS and PFS (P < 0.001, P < 0.001, P = 0.007 and P = 0.001, P = 0.002, P < 0.001, respectively). Using these three variables, we made a new prognostic model which classified patients on risk as follows: low, no adverse factors; intermediate, 1 factor; or high, 2-3 factors. The new prognostic model could stratify the three groups for OS and PFS better than either international prognostic index or prognostic index of PTCL-u, and showed statistical significance in PTCL, not otherwise specified. This study suggests that whole blood EBV-DNA is related with aggressive clinical characteristics and inferior survival. The new prognostic model, which incorporates EBV-DNA, could better stratify PTCL patients.
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Programmed cell death 1 (PD-1) and its ligands PD-L1/PD-L2 have been shown to mediate immune evasion in various cancers, but their prognostic implications in patients with primary central nervous system lymphoma (PCNSL) are poorly understood. Therefore, we analyzed 76 PCNSL patients at initial diagnosis who were treated homogenously with high-dose methotrexate-based chemotherapy, and evaluated the prognostic roles of high immunohistochemical PD-1, PD-L1, and PD-L2 expression. The cut-off values for high PD-1 (≥ 70 cells/high power field [HPF]), PD-L1 (≥ 100 cells/HPF), and PD-L2 (≥ 100 cells/HPF) were determined by the area under the receiver operating characteristic curve. Expression of PD-1, PD-L1, and PD-L2 was high in 7.9%, 13.2%, and 42.1% patients, respectively. High PD-1, (P = 0.007) and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic scoring (P = 0.019) were independently associated with inferior overall survival on multivariate analysis. High PD-1 also remained an independent prognostic factor for inferior progression-free survival (P = 0.028), as did MSKCC prognostic scoring (P = 0.041) on multivariate analysis. However, there were no differences in survival according to the expression levels of PD-L1/PD-L2 in PCNSL tumor microenvironment. Our results suggest that PD-1 may be considered a biomarker and potential therapeutic target in PCNSL.
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As DNA databases continue to grow and international cooperation increases, forensic STR loci have expanded to increase the discriminatory power and inter-database compatibility. Current capillary electrophoresis (CE) and/or massively parallel sequencing (MPS)-based commercial STR analysis systems reflect such changing trends of expanding STR loci. Due to the general gains of larger multiplexing and the detection of sequence variation, the application of MPS technology to STR analysis has further improved discrimination and is expected to aid in mixture interpretation by increasing the effective number of alleles. However, high-throughput analysis has rarely been reported for forensic DNA databasing. In this study, we present the sequencing results from 250 Korean samples at 23 commonly used STR loci (D1S1656, TPOX, D2S441, D2S1338, D3S1358, FGA, CSF1PO, D5S818, D6S1043, D7S820, D8S1179, D10S1248, TH01, vWA, D12S391, D13S317, Penta E, D16S539, D18S51, D19S433, D21S11, Penta D, and D22S1045) using an in-house assay designed for MPS. All amplicons in the multiplex exhibited a size range of 77 to 217 base pairs, and the barcoded library for the MPS run was easily prepared using a PCR-based library preparation method followed by sequencing on a MiSeq System (Illumina). We compared the STR genotyping results with those obtained using CE and scrutinized the sequence variations in both the targeted STR and flanking regions. MPS results of 23 autosomal STRs were 99.97% concordant with those of CE results. D12S391 and D21S11 exhibited, respectively, the highest number of alleles and genotypes by the MPS analysis. Single nucleotide polymorphisms and insertion and deletions (Indels) were observed in the flanking regions of D1S1656, D2S441, D5S818, D7S820, D13S317, D16S539, D21S11, and Penta D. Consequently, an MPS analysis of an expanded set of STRs, as demonstrated in the population statistics of a Korean population, will be of great practical use in forensic genetics.
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Pueblo Asiatico/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación INDEL , Repeticiones de Microsatélite , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Genotipo , Humanos , Reacción en Cadena de la Polimerasa , República de CoreaRESUMEN
Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume). Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006). Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001). Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or adjunct to other therapies.
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Neovascularización Coroidal/prevención & control , Itraconazol/uso terapéutico , Coagulación con Láser/efectos adversos , Animales , Neovascularización Coroidal/etiología , Ensayo de Inmunoadsorción Enzimática , Angiografía con Fluoresceína , Inyecciones Intravítreas , Itraconazol/administración & dosificación , Masculino , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The major prognostic determinant of immunoglobulin light chain (AL) amyloidosis is cardiac involvement. However, the role of interventricular septal thickness (IVST), which reflects the extent of cardiac involvement, remains unclear. Therefore, we analyzed 77 patients with newly diagnosed AL amyloidosis and evaluated the prognostic role of IVST. Fifty patients (64.9%) had cardiac involvement and 17 patients (22.1%) showed IVST >15mm. Among all patients, the revised Mayo Clinic Stage III-IV and IVST >15mm were independently associated with inferior overall survival (OS) in a multivariable analysis. IVST >15mm was also adversely prognostic for OS in a subgroup of advanced-stage (revised Mayo Clinic stage III-IV) patients in a multivariable analysis (P<0.001). Furthermore, advanced-stage patients with IVST >15mm did not show survival benefit from treatment with bortezomib-based regimens and/or autologous stem-cell transplantation (ASCT). Our study demonstrated that IVST >15mm is adversely prognostic independent of the revised Mayo Clinic staging system in patients with AL amyloidosis. In addition, the degree of IVST might be used as a useful prognostic indicator that can guide the management of patients with AL amyloidosis especially at an advanced stage.
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Amiloidosis/diagnóstico , Tabiques Cardíacos/patología , Adulto , Anciano , Amiloidosis/complicaciones , Amiloidosis/patología , Femenino , Neoplasias Cardíacas/patología , Ventrículos Cardíacos/patología , Humanos , Cadenas Ligeras de Inmunoglobulina , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
The goal of this study was to reassess serum alkaline phosphatase (ALP) as tumor marker in osteosarcoma. We retrospectively examined serum ALP levels at diagnosis, every therapeutic step (neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy), metastasis, and follow-up and analyzed the role of ALP as tumor marker in 210 osteosarcomas. The diagnostic performances of ALP were validated with pathology-proven 899 other primary bone lesions. Elevated ALP at diagnosis was associated with inferior overall survival (OS) (Log Rank P < 0.001) and disease-free survival (Log Rank P = 0.005) and independently significant for OS in multivariate analysis (hazard ratio [HR]=2.12, P = 0.032). During therapy, the ALP level significantly changed according to therapeutic steps (P < 0.001 for patients ≥15 years old, P < 0.001 for patients <15 years old) and survival (P = 0.015 for ≥15 years, P = 0.002 for <15 years), and the response of ALP to therapy and survival were associated (P = 0.042 for ≥15 years, P = 0.036 for <15 years). Initial ALP level was linearly correlated with tumor burden (total tumor volume; P = 0.016 for ≥15 years, bone tumor volume; P = 0.012 for ≥15 years). The sensitivity and specificity of ALP on diagnosis were 53.2% (95% Confidence Interval [CI]: 0.475-0.586) and 90.1% (95% CI: 0.888-0.913). The sensitivity of ALP on metastasis was 53.2% (95% CI: 0.431-0.624), and the specificity was 78.2% (95% CI: 0.720-0.839) at15 months postoperative and 90.0% (95% CI: 0.824-0.952) at 3 years postoperative. Serum ALP was found to be a valuable tumor marker with high specificity in osteosarcoma.
Asunto(s)
Fosfatasa Alcalina/sangre , Biomarcadores de Tumor/sangre , Neoplasias Óseas/sangre , Osteosarcoma/sangre , Adolescente , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Osteosarcoma/diagnóstico , Osteosarcoma/patología , Sensibilidad y Especificidad , Carga TumoralRESUMEN
The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P = 0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among patients who did not receive upfront ASCT (n = 60), but not in patients who received upfront ASCT. The expression of FoxP3 was not significantly associated with survival. Therefore, we identified a prognostic significance of high CD68 expression in PCNSL, which suggests a need for further clinical trials and biological studies on the role of PCNSL tumor microenvironment.