Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Leukemia ; 34(1): 100-114, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31197259

RESUMO

Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in Toll-like receptor (TLR) signal transduction and innate immune responses. Recruitment and subsequent activation of IRAK4 upon TLR stimulation is mediated by the myeloid differentiation primary response 88 (MYD88) adaptor protein. Around 3% of chronic lymphocytic leukemia (CLL) patients have activating mutations of MYD88, a driver mutation in this disease. Here, we studied the effects of TLR activation and the pharmacological inhibition of IRAK4 with ND2158, an IRAK4 competitive inhibitor, as a therapeutic approach in CLL. Our in vitro studies demonstrated that ND2158 preferentially killed CLL cells in a dose-dependent manner. We further observed a decrease in NF-κB and STAT3 signaling, cytokine secretion, proliferation and migration of primary CLL cells from MYD88-mutated and -unmutated cases. In the Eµ-TCL1 adoptive transfer mouse model of CLL, ND2158 delayed tumor progression and modulated the activity of myeloid and T cells. Our findings show the importance of TLR signaling in CLL development and suggest IRAK4 as a therapeutic target for this disease.

2.
Cancer Sci ; 111(2): 749-759, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31849147

RESUMO

The revised WHO classification newly defined the entities "High-grade B-cell lymphoma with MYC and BCL2, and/or BCL6 rearrangements (HGBL-DH/TH)" and "HGBL, NOS." Standard immunochemotherapy for diffuse large B-cell lymphoma (DLBCL), R-CHOP, is insufficient for HGBL patients, and there are currently no optimized therapeutic regimens for HGBL. We previously reported that CCND3, which encodes cyclin D3, harbored high mutation rates in Burkitt lymphoma (BL), HGBL and a subset of DLBCL. Furthermore, the knockdown of cyclin D3 expression was toxic to germinal center (GC)-derived B-cell lymphomas. Thus, the fundamental function of cyclin D3 is important for the pathogenesis of GC-derived B-cell lymphoma. We herein used two structurally different CDK4/6 inhibitors, palbociclib and abemaciclib, and examined their suppressive effects on cell proliferation and their ability to induce apoptosis in various aggressive B-cell lymphoma cell lines. The results obtained demonstrated that abemaciclib more strongly suppressed cell proliferation and induced apoptosis in GC-derived B-cell lymphoma cell lines than the control, but only slightly inhibited those features in activated B-cell (ABC)-like DLBCL cell lines. Palbociclib exerted partial or incomplete effects compared with the control and the effect was intermediate between abemaciclib and the control. Moreover, the effects of abemaciclib appeared to depend on cyclin D3 expression levels based on the results of the expression analysis of primary aggressive B-cell lymphoma samples. Therefore, abemaciclib has potential as a therapeutic agent for aggressive GC-derived B-cell lymphomas.

3.
J Exp Clin Cancer Res ; 38(1): 446, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676012

RESUMO

BACKGROUND: NOTCH1 gene mutations in mantle cell lymphoma (MCL) have been described in about 5-10% of cases and are associated with significantly shorter survival rates. The present study aimed to investigate the biological impact of this mutation in MCL and its potential as a therapeutic target. METHODS: Activation of Notch1 signaling upon ligand-stimulation and inhibitory effects of the monoclonal anti-Notch1 antibody OMP-52M51 in NOTCH1-mutated and -unmutated MCL cells were assessed by Western Blot and gene expression profiling. Effects of OMP-52M51 treatment on tumor cell migration and tumor angiogenesis were evaluated with chemotaxis and HUVEC tube formation assays. The expression of Delta-like ligand 4 (DLL4) in MCL lymph nodes was analyzed by immunofluorescence staining and confocal microscopy. A MCL mouse model was used to assess the activity of OMP-52M51 in vivo. RESULTS: Notch1 expression can be effectively stimulated in NOTCH1-mutated Mino cells by DLL4, whereas in the NOTCH1-unmutated cell line JeKo-1, less effect was observed upon any ligand-stimulation. DLL4 was expressed by histiocytes in both, NOTCH1-mutated and -unmutated MCL lymph nodes. Treatment of NOTCH1-mutated MCL cells with the monoclonal anti-Notch1 antibody OMP-52M51 effectively prevented DLL4-dependent activation of Notch1 and suppressed the induction of numerous direct Notch target genes involved in lymphoid biology, lymphomagenesis and disease progression. Importantly, in lymph nodes from primary MCL cases with NOTCH1/2 mutations, we detected an upregulation of the same gene sets as observed in DLL4-stimulated Mino cells. Furthermore, DLL4 stimulation of NOTCH1-mutated Mino cells enhanced tumor cell migration and angiogenesis, which could be abolished by treatment with OMP-52M51. Importantly, the effects observed were specific for NOTCH1-mutated cells as they did not occur in the NOTCH1-wt cell line JeKo-1. Finally, we confirmed the potential activity of OMP-52M51 to inhibit DLL4-induced Notch1-Signaling in vivo in a xenograft mouse model of MCL. CONCLUSION: DLL4 effectively stimulates Notch1 signaling in NOTCH1-mutated MCL and is expressed by the microenvironment in MCL lymph nodes. Our results indicate that specific inhibition of the Notch1-ligand-receptor interaction might provide a therapeutic alternative for a subset of MCL patients.

4.
Esophagus ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595395

RESUMO

BACKGROUND: Magnifying endoscopy has demonstrated dramatic morphologic changes in the surface microvasculature of superficial esophageal squamous cell carcinoma (ESCC) according to the depth of invasion. We investigated the mechanism of angiogenesis in early-stage ESCC by examining the expression of vascular endothelial growth factor (VEGF)-A and chondromodulin (ChM)-1. METHODS: Using 41 samples of superficial esophageal cancer (EP and LPM 19 cases, MM or deeper 22 cases) and 7 samples of regenerative squamous epithelium, the expression of VEGF-A and ChM-1 was examined in relation to the histological grade or morphology of the surface microvasculature demonstrated by magnifying endoscopy (types A, B, and C correspond to types A, B1, and B2 and B3 of the magnifying endoscopic classification of the Japan Esophageal Society, respectively). We also investigated the correlation between CD31-positive microvessel density (MVD) and VEGF-A or ChM-1 expression. RESULTS: In normal squamous epithelium, regenerative squamous epithelium, EP and LPM cancer, and MM or deeper cancer, the positivity rates for VEGF-A and ChM-1 were 0%, 85.7%, 52.6% and 90.9%, respectively, and 48.5%, 71.4%, 73.7% and 23.8%, respectively. The VEGF-A and ChM-1 positivity rates in type B or type C vasculature were 70.0% and 76.2%, respectively, and 75.0% and 19.0%, respectively. The expression of neither VEGF-A nor ChM-1 in cancer cells was correlated with MVD (P = 0.19 and 0.68, respectively), whereas that of VEGF-A in stromal mononuclear cells (SMCs) was significantly correlated with MVD (P = 0.04). CONCLUSION: Angiogenesis at the early stage of ESCC progression is configured by the balance between accelerator (angiogenic factors from both cancer cells and SMCs) and brake (angiogenic inhibitor) factors.

5.
World J Surg Oncol ; 17(1): 151, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462247

RESUMO

BACKGROUND: While calcification of thymoma is common, "eggshell" calcification is rare. We report a case of an eggshell calcified thymoma that "hatched" after 4 years of follow-up. Pathologically, it revealed that sarcoidosis accompanied this case of thymoma, which might cause in calcification. CASE PRESENTATION: The patient was a 68-year-old female. A 20-mm anterior mediastinal nodule completely covered with calcification was noted in an annual health check-up. However, as the nodule did not change during 6 months of follow-up, she discontinued regular examinations. Four years later, an abnormality in her chest X-ray was noted again. The tumor grew outside the calcification to reach 63 mm. She underwent resection of this anterior mediastinal tumor. Pathologically, the tumor was diagnosed as thymoma of type B1 in the WHO classification. The histology of the tumor inside and outside of the calcification was not different, suggesting that the tumor grew from the inside of the calcification. The calcification was located within the fibrotic capsule of thymoma. Sarcoidosis also presented in her lung and mediastinal lymph nodes. CONCLUSIONS: Although the mechanism of calcification of the capsule was not clear, sarcoidosis might be related to this case because macrophage accumulation and altered lipid metabolism in sarcoidosis present with similar dystrophic calcification.

6.
Leuk Lymphoma ; 60(10): 2508-2515, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30947579

RESUMO

Methotrexate (MTX) is one of the potent drugs for autoimmune diseases (ADs), especially for rheumatoid arthritis. Recent studies suggest that MTX should be immediately withdrawn when patients with AD develop lymphoproliferative disorder (LPD). However, biopsy cannot be performed for diagnosis because LPD regresses quickly after MTX withdrawal, thus making clinical MTX-LPD (c-MTX-LPD) challenging to diagnose. In this study, among the 28 patients with c-MTX-LPD, seven developed a proven LPD (p-LPD) after suspicious LPD (s-LPD) regression, six of which were Hodgkin lymphoma. Four of seven patients with p-LPD + died, whereas all patients with p-LPD- survived. The clinical manifestations indicative of p-LPD include fever, elevated serum C-reactive protein level, and soluble interleukin-2 receptor level. Anti-AD drugs did not appear to affect the pathogenesis of p-LPD development. P-LPD was not observed after 3 years from the time of s-LPD regression.

7.
Pathol Int ; 69(3): 155-159, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30719810

RESUMO

Anaplastic large cell lymphoma (ALCL) with TP63 rearrangement is a new entity and has the most dismal prognosis in all types of ALCL. This might be due to the resulting fusion protein having N-terminal truncated p63 with high oncogenic ability. Since this N-terminal domain has the function of tumor suppressor activity, the mechanism for high oncogenic capacity is thought to be the dominant negative function. Here, we report two ALCL cases with TP63 rearrangement that was each given too short a prognosis (Case 1 and 2: four and six months) in spite of intensive treatment. Immunohistochemically, p63 was highly expressed, and a sprit signal was detected using a TP63 break apart fluorescence in situ hybridization (FISH) in each case. Additionally, a poor prognostic marker of ALCL, all cytotoxic molecules (TIA-1, Granzyme B, and Perforin) were also expressed in almost all ALCL cells. Taken together, we suggest that not only the dominant negative function of N-truncated p63 but also the effect of cytotoxic molecules may influence the dismal prognosis of ALCL with TP63 rearrangement.


Assuntos
Doença de Hodgkin/patologia , Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/patologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Idoso , Feminino , Granzimas , Doença de Hodgkin/diagnóstico , Humanos , Hibridização in Situ Fluorescente/métodos , Linfoma Anaplásico de Células Grandes/diagnóstico , Masculino , Prognóstico , Proteínas Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Antígeno-1 Intracelular de Células T/metabolismo
8.
Case Rep Urol ; 2018: 1605102, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854548

RESUMO

Cystic nodal metastasis of renal cell carcinoma is very rare. The pathogenesis of cystic nodal metastasis is thought to involve obstruction of a lymphoid vessel draining the kidney by tumor cells and retrograde metastasis from the primary site to the lymph node along the lymphatic vessels. In this study, a surgical case of small renal cell carcinoma with retroperitoneal cystic nodal metastasis is reported.

9.
Esophagus ; 15(1): 19-26, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29892805

RESUMO

BACKGROUND: The relationship between thymidine phosphorylase (TP) and angiogenesis at the early stage of esophageal squamous cell carcinoma has been unclear. METHODS: Using 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer, microvessel density (MVD) was estimated using immunostaining for CD34 and CD105. TP expression was also evaluated in both cancer cells and stromal monocytic cells (SMCs). We then investigated the correlation between MVD and TP expression in both cancer cells and SMCs. RESULTS: On the basis of the above parameters, MVD was significantly higher in cancerous lesions than in normal squamous epithelium. In terms of CD34 and CD105 expression, MVD showed a gradual increase from normal squamous epithelium, to low-grade intraepithelial neoplasia, and then to M1 and M2 cancer, and M3 or deeper cancer. M1 and M2 cancer showed overexpression of TP in both cancer cells and SMCs. There was no significant correlation between TP expression in cancer cells and MVD estimated from CD34 (rS = 0.16, P = 0.21) or CD105 (rS = 0.05, P = 0.68) expression. Significant correlations were found between TP expression in SMCs and CD34-related (rS = 0.46, P < 0.001) and CD105-related (rS = 0.34, P < 0.01) MVD. In M3 or deeper cancers, there were no significant correlations between TP expression in cancer cells or SMCs and venous invasion, lymphatic invasion, and lymph node metastasis. CONCLUSION: TP expression is activated in both cancer cells and stromal monocytic cells at the very early stage of ESCC progression. TP expression in SMCs, rather than in cancer cells, is significantly correlated with angiogenesis.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Neoplasias Esofágicas/enzimologia , Neovascularização Patológica/enzimologia , Timidina Fosforilase/fisiologia , Antígenos CD34/metabolismo , Carcinoma de Células Escamosas/irrigação sanguínea , Progressão da Doença , Endoglina/metabolismo , Epitélio/irrigação sanguínea , Epitélio/enzimologia , Neoplasias Esofágicas/irrigação sanguínea , Carcinoma de Células Escamosas do Esôfago , Esôfago/irrigação sanguínea , Esôfago/enzimologia , Humanos , Microvasos/patologia , Lesões Pré-Cancerosas/enzimologia , Células Estromais/enzimologia , Timidina Fosforilase/metabolismo
11.
Leuk Lymphoma ; 59(5): 1143-1152, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28877615

RESUMO

Although recent accumulative data reveal the clinicopathogenesis of regression in methotrexate-induced lymphoproliferative disorders (MTX-LPDs), the precise understanding including this category remains controversial. In this study, we analyzed 62 patients with MTX-LPD. Forty-three patients showed regression (Reg group), with high rates of Hodgkin lymphoma (HL) and LPD (90 and 88%, respectively). Among the 43 patients of the Reg group, 14 patients (33%) relapsed. The median duration before relapse in the Reg group was 10.6 months. Although the difference of OS between the Reg and Non-Reg groups was not significantly different, relapse-free patients in the Reg group had a superior overall survival (OS). MTX duration had a significant impact on Epstein-Barr virus (EBV) infection (p = .00131). Furthermore, EBV infection was significantly related to clinical manifestations, including spleen invasion, in the regression phenomenon. Some human leukocyte antigens (HLA) alleles might affect MTX-LPD development via EBV infection, although A*2402 and DRB1*0405 might be affected as fundamental factors.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/isolamento & purificação , Transtornos Linfoproliferativos/patologia , Metotrexato/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Humanos , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Taxa de Sobrevida
12.
Expert Opin Drug Discov ; 12(10): 1041-1052, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28776453

RESUMO

INTRODUCTION: Next generation sequencing has provided a comprehensive understanding of the mutational landscape in chronic lymphocytic leukemia (CLL), and new drivers have been identified. Some of these drivers could be pharmacologically targeted to choose the most effective personalized therapy in each CLL patient. Areas covered: In this article, the authors uncover the potential role of new targeted therapies against the most recurrent mutations in CLL as well as the recently approved therapies. The authors also provide their expert opinion and give their perspectives for the future. Expert opinion: The development of more personalized therapies is of interest to clinicians as a system to enhance the duration of treatment response and to extend the survival and quality of life of CLL patients. The main challenge, however, will be to translate the preclinical results into the clinics. Therefore, the designing and execution of clinical trials focused on molecular drivers are the need of the hour.


Assuntos
Antineoplásicos/farmacologia , Descoberta de Drogas/métodos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Animais , Desenho de Drogas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Terapia de Alvo Molecular , Mutação , Medicina de Precisão , Qualidade de Vida , Taxa de Sobrevida
13.
Int J Oncol ; 51(2): 579-586, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28714514

RESUMO

The development and acquisition of multiple drug resistance in cancer cells remain a major obstacle in the treatment of bladder cancer. Nuclear translocation of Y box binding-1 (YB-1), which is a member of a family of DNA-binding proteins that contain a cold shock domain, plays a significant role in the acquisition of drug resistance by upregulating expression of the multidrug resistance-1 (MDR-1) gene product, p-glycoprotein. The tumor suppressor protein p53 is thought to be essential for nuclear translocation of YB-1. We hypothesized that nuclear translocation of YB-1 might be associated with drug resistance of bladder cancer with an abnormality of the TP53 gene that results in a mutated p53 protein. To test this hypothesis, we analyzed the association of YB-1 with drug resistance of TP53-mutated bladder cancer, including immunohistochemical analysis of YB-1, p-glycoprotein and p53 in vivo as well as the function of YB-1 nuclear translocation and regulation of its translocation by p53 in vitro. Additionally, we examined the association between the nuclear translocation of YB-1 and gemcitabine, a major anticancer-drug for bladder cancer, in cancer cell lines. Nuclear expression of YB-1 was correlated with the expression of p-glycoprotein and p53 in bladder cancer cases (p<0.05). In vitro, both introduction of TP53 and gemcitabine induced nuclear translocation of YB-1. These data indicate that YB-1 translocates to the nucleus coordinately with p53 expression and is involved in gemcitabine resistance in bladder cancer. Nuclear expression of YB-1 is important for resistance to chemotherapy including gemcitabine in TP53-mutated bladder cancer.


Assuntos
Núcleo Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Bexiga Urinária/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Resistência a Múltiplos Medicamentos , Feminino , Células HeLa , Humanos , Células MCF-7 , Masculino , Mutação , Proteína Supressora de Tumor p53/genética , Neoplasias da Bexiga Urinária/genética
14.
J Clin Exp Hematop ; 56(3): 165-169, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28331131

RESUMO

Recently, attention has been focused on methotrexate-induced lymphoproliferative disease (MTX-LPD), and atypical phenotypes are occasionally documented. We encountered two patients with rheumatoid arthritis (RA) who were diagnosed with non-specific LPD (LPD-nos). Biopsy samples were not obtained during the initial examination when the LPD development was discovered, and the patients achieved a complete response after MTX cessation (case 1) or steroid pulse therapy (case 2). However, the tumors flared up 1.5 years later, and LPD-nos was determined following biopsies of the lymph node (LN, case 1) and liver (case 2). Prednisolone was subsequently administered instead of chemotherapy; however, multiple masses, including in the spine (case 1), and severe icterus with liver dysfunction (case 2) were exacerbated within a few months. Although the re-biopsy of LN proved the presence of HL and radiation followed by aggressive chemotherapy rescued the patient (case 1), the superficially accessible biopsy site was not found, and autopsy finally revealed HL (case 2). In both cases, the underlying pathogenesis along with the B symptoms and laboratory abnormalities suggested MTX-LPD, HL in particular. Therefore, even if the pathological diagnosis does not confirm the specific LPD subtype, the administration of aggressive chemotherapy should be considered if the LPD activity flares severely.


Assuntos
Artrite Reumatoide/complicações , Doença de Hodgkin/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Recidiva , Indução de Remissão/métodos
15.
Graefes Arch Clin Exp Ophthalmol ; 255(5): 885-891, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28102455

RESUMO

PURPOSE: LR11 (also called SorLA or SORL1) is a migration regulator of adherent cells with the immature proliferative phenotype. The present study investigated the clinical and pathological involvement of the soluble form of LR11 (sLR11) in the idiopathic epiretinal membrane (iERM). METHODS: The subjects were 51 patients with iERM (24 cellophane macular reflex (CMR) and 27 preretinal macular fibrosis (PMF)) and 45 patients with macular holes as age and sex-matched controls. Vitreous sLR11 and transforming growth factor (TGF)ß2 levels were measured by ELISA. RESULTS: The sLR11 levels in the vitreous fluids of patients with iERM (20.2 ± 8.1 ng/mL) were significantly higher than those in controls (11.4 ± 4.7 ng/mL). Among the patients with iERM, the vitreous sLR11 levels were significantly higher in PMF (23.6 ± 8.2 ng/mL), than those in CMR (16.5 ± 5.9 ng/mL). Multivariate regression analysis of the studied factors showed that sLR11 was a unique factor independently contributing to the discrimination of the iERM patients against the control subjects (odds ratio [OR] 1.35 per 1-ng/mL increase, 95% CI 1.09-1.67; P = 0.004). ROC analysis showed that the sensitivity and the specificity of sLR11, but not of other studied factors, categorized into the rank of moderate accuracy. Finally, there was a positive correlation (R = 0.588; P = 0.003) between the vitreous levels of sLR11 and TGFß2 using the available samples. CONCLUSIONS: sLR11 levels in vitreous fluids were specifically increased in patients with iERM, suggesting the involvement in the pathology of proliferative and migrating cells for the development of iERM.


Assuntos
Membrana Epirretiniana/metabolismo , Proteínas Relacionadas a Receptor de LDL/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Corpo Vítreo/metabolismo , Idoso , Biomarcadores/metabolismo , Movimento Celular , Ensaio de Imunoadsorção Enzimática , Membrana Epirretiniana/patologia , Feminino , Humanos , Masculino , Proteínas do Tecido Nervoso , Estudos Retrospectivos , Fator de Crescimento Transformador beta2/metabolismo , Corpo Vítreo/patologia
16.
Endoscopy ; 49(2): 176-180, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27842421

RESUMO

Background and study aims We report the features of a newly developed endocytoscopy system (ECS), the GIF-Y0074. Patients and methods The GIF-Y0074 offers high-definition resolution with a consecutive increase of magnification to × 500. Using ECS, we observed 32 cases of esophageal squamous cell carcinoma (ESCC), 11 cases of gastric cancer, and five cases of duodenal adenoma. Results The images of cells obtained using the GIF-Y0074 at maximum magnification were brighter and clearer than those obtained with previous ECS systems. For diagnosis of ESCC, clearer visualization of the nucleus made nuclear abnormality easier to recognize. Cancer cells were visualized in 10/11 cases of gastric cancer, but removal of mucus still remained a problem. Duodenal adenomas were found to have atypical cells with villi and tubules at the mucosal surface, thus assisting their histological diagnosis in vivo. Conclusion The GIF-Y0074 is an excellent ECS in terms of ease of use, satisfactory resolution, and magnification power, and therefore achieves a level of utility that makes its commercial release justifiable. This ECS heralds a new era of endoscopic and histological diagnosis.


Assuntos
Adenoma/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Duodenais/patologia , Endoscópios Gastrointestinais , Endoscopia Gastrointestinal , Neoplasias Esofágicas/patologia , Microscopia Nuclear , Neoplasias Gástricas/patologia , Endoscopia Gastrointestinal/instrumentação , Endoscopia Gastrointestinal/métodos , Desenho de Equipamento , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Microscopia Nuclear/instrumentação , Microscopia Nuclear/métodos , Reprodutibilidade dos Testes
17.
Leuk Lymphoma ; 57(1): 161-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25860238

RESUMO

The interaction between tumor cells and the tumor microenvironment is essential in the development and progression of diffuse large B-cell lymphoma (DLBCL). Loss of human leukocyte antigen DR (HLA-DR) in DLBCL is a robust adverse prognostic marker. We evaluated the immunohitochemical expression of HLA-DR in lymphoma and the biologic implications of the loss of HLA-DR. The loss of HLA-DR correlated with clinical stage (p < 0.05), International Prognosis Index (p < 0.05), soluble interleukin-2 receptor (p < 0.05) and poor outcome in patients with DLBCL, especially among elderly patients. Flow cytometry analysis of the infiltrating T-cells showed that the mean CD4 + CD25 +/CD8 ratio of the infiltrating T-cells was higher in the HLA-DR positive group than in the HLA-DR negative group (p < 0.05). These data suggest that loss of HLA-DR expression in DLBCL decreases the ratio of helper T-cell within the T-cell population in the tumor microenvironment and might contribute to escape from immunosurveillance.


Assuntos
Antígenos HLA-DR/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Microambiente Tumoral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Feminino , Expressão Gênica , Antígenos HLA-DR/genética , Humanos , Imunofenotipagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Adulto Jovem
18.
Int Surg ; 100(4): 733-43, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25875558

RESUMO

Using immunohistochemical staining, the present study was conducted to examine whether cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) affect angiogenesis in early-stage esophageal squamous cell carcinoma (ESCC). We also analyzed the correlation between these two factors. Cyclooxygenase 2, iNOS, and angiogenesis in early-stage ESCC are unclear. Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia (LGIN), and 45 samples of superficial esophageal cancer, we observed the expression of COX-2 and iNOS. We then investigated the COX-2 and iNOS immunoreactivity scores and the correlation between COX-2 or iNOS scores and microvessel density (MVD) using CD34 or CD105. The intensity of COX-2 or iNOS expression differed significantly according to histological type (P < 0.001). The scores of COX-2 and iNOS were lowest for normal squamous epithelium, followed in ascending order by LGIN, carcinoma in situ and tumor invading the lamina propria mucosae (M1-M2 cancer); and tumor invading the muscularis mucosa (M3) or deeper cancer. The differences were significant (P < 0.001). Cancers classified M1-M2 (P < 0.01 and P < 0.05, respectively); M3; or deeper cancer (P < 0.01) had significantly higher COX-2 and iNOS scores than normal squamous epithelium. There was a significant correlation between COX-2 and iNOS scores (P < 0.001, rs = 0.51). Correlations between COX-2 score and CD34-positive MVD or CD105-positive MVD were significant (rs = 0.53, P < 0.001; rs = 0.62, P < 0.001, respectively). Inducible nitric oxide synthase score was also significantly correlated with CD34 MVD and CD105 MVD (rs = 0.45, P < 0.001; rs = 0.60, P < 0.001, respectively). Chemoprevention of COX-2 or iNOS activity may blunt the development of ESCC from precancerous lesions.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Ciclo-Oxigenase 2/metabolismo , Neoplasias Esofágicas/enzimologia , Neovascularização Patológica/enzimologia , Óxido Nítrico Sintase Tipo II/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Humanos , Imuno-Histoquímica , Estadiamento de Neoplasias
19.
Rinsho Ketsueki ; 56(1): 9-15, 2015 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-25745961

RESUMO

Primary cardiac lymphoma is extremely rare and is associated with a poor prognosis. In most cases, cardiac involvement occurs as a late symptom and the diagnosis is thus delayed. We herein report a 35-year-old woman with cardiac diffuse large B-cell lymphoma (DLBCL) with breast infiltration. The patient was admitted to our hospital based on an initial presentation with dyspnea on exertion, chest pain, and a hard mass of the left breast. Echocardiography revealed a mass in the right atrium wall and interatrial septum, and massive pericardial effusion. ECG showed atrioventoricular block. We promptly performed a needle biopsy of the breast mass, which showed CD5-positive DLBCL, non-GCB type. The serum HIV reaction was negative. We thus diagnosed this patient as having cardiac and breast CD5-positive DLBCL, stage IVA, based on the massive pericardial effusion. The patient's prognosis was apparently poor. Therefore, she received 3 cycles of R-CHOP chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT), resulting in a complete response. In general, cardiac lymphoma is associated with high mortality and has a poor prognosis. This case demonstrates that rapid and appropriate diagnosis, and immediate intensive chemotherapy followed by PBSCT might be necessary for the treatment of extranodal lymphoma indicative of a poor prognosis.


Assuntos
Neoplasias da Mama/terapia , Neoplasias Cardíacas/terapia , Linfoma Difuso de Grandes Células B/terapia , Derrame Pericárdico/terapia , Adulto , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Feminino , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/patologia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Estadiamento de Neoplasias , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/etiologia , Transplante de Células-Tronco de Sangue Periférico , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA