RESUMO
Objective:To develop the anti-CD30 monoclonal antibody 64Cu-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD30 and visualize CD30 expression in lymphoma non-invasively. Methods:The CD30 expression levels of 5 cell lines (Karpas299, Raji, Daudi, Ramos, and U266) were assessed by Western blot. Cell lines with high and low CD30 expression were selected for flow cytometry to evaluate the specific binding affinity of anti-CD30 monoclonal antibody. Thirteen NSG mice were used to established CD30 positive and negative subcutaneous xenograft models. 64Cu-NOTA-CD30 was obtained and 64Cu-NOTA-immunoglobulin (Ig)G was used as the control. ImmunoPET imaging was performed 2, 24, and 48 h after the injection of 64Cu-NOTA-CD30 or 64Cu-NOTA-IgG. Finally, the biodistribution studies were conducted. Repeated-measures analysis of variance and Bonferroni test were conducted for comparison. Results:Karpas299 showed the highest CD30 expression, while Raji showed the lowest. Flow cytometry showed specific binding affinity of the anti-CD30 monoclonal antibody to the Karpas299 cell line. The radiochemical purities of the probes were both higher than 95%. In microPET, the 64Cu-NOTA-CD30 uptake of Karpas299 xenograft tumors increased over time, with (11.46±0.58), (17.60±1.16) and (19.46±0.99) percentage activity of injection dose per gram of tissue (%ID/g) at 2, 24 and 48 h respectively. The contrast to normal tissue was good at 48 h, with the tumor/heart (blood) ratio of 2.20±0.22. The uptake of 64Cu-NOTA-CD30 in Karpas299 tumor at 48 h after injection was significantly higher than that in Raji tumor ((6.10±1.03) %ID/g) and 64Cu-NOTA-IgG in Karpas299 tumor ((5.12±0.89) %ID/g; F=290.99, t values: 19.65 and 22.25, all P<0.001). The uptake of 64Cu-NOTA-CD30 and the control probe in the heart and liver decreased over time in all groups. Ex vivo biodistribution at 48 h was mainly consistent with the results of microPET in vivo. Conclusions:64Cu-NOTA-CD30 is able to visualize the expression level and distribution of CD30 non-invasively. It is promising to be applied for screening the beneficial groups and evaluating efficacy for CD30-targeted immunotherapy.
RESUMO
Objective:To investigate clinicopathological features and prognosis of transformed mycosis fungoides (TMF) .Methods:A retrospective analysis was performed on clinicopathological data collected from 24 patients with TMF, as well as on flow cytometry results of 16 peripheral blood samples obtained from 11 of the 24 patients, who visited Hospital of Dermatology, Chinese Academy of Medical Sciences between 2014 and 2020.Results:Among the 24 patients, 11 were males and 13 were females. Their average age at diagnosis of TMF was 50.0 years (range: 18 - 77 years), and patients with early-stage TMF (9 cases) and tumor-stage TMF (15 cases) were aged 44.8 and 52.6 years on average, respectively. The average time interval from diagnosis of MF to large cell transformation was 3.7 years, and 8 patients were diagnosed with TMF at the initial visit. Histopathologically, large cells infiltrated in a diffuse pattern in 20 cases, as well as in a multifocal pattern in 4, and the proportion of large cells in 7 cases was greater than 75%. Immunohistochemically, 18 patients showed positive staining for CD30, and the proportion of CD30-positive large cells was greater than 75% in 9; negative staining for CD30 was observed in 6. Flow cytometry of 16 peripheral blood samples showed the presence of cell subsets expressing clonal T cell receptor (TCR) -vβ in 2 of 4 patients with early-stage TMF and 10 of 12 with tumor-stage TMF, and tumor cells with higher forward scatter than normal lymphocytes were detected in 16 samples. During the follow-up, among the patients with early-stage TMF, 3 progressed to tumor-stage TMF 3.3 years on average after large cell transformation, 1 progressed to erythrodermic MF in stage IIIA, and the other 4 still showed an indolent course; among the patients with tumor-stage TMF, 1 progressed to stage-IV TMF, and 5 died 3.3 (1.5 - 6) years after large cell transformation.Conclusion:Large cell transformation may occur in patients with MF in any stage, some patients have poor prognosis, so close follow-up is needed for patients with TMF.
RESUMO
Objective To deepen the understanding of curative effect and adverse drug reaction of brentuximab vedotin in the treatment of Hodgkin's lymphoma.Methods One case of newly diagnosed Hodgkin's lymphoma who treated with brentuximab vedotin was collected.The clinical features,laboratory examination,treatment procedure,prognosis were analyzed,and the relevant literature was reviewed.Results The patient was twenty years old,female,found the right neck masses for five days,diagnosed with Hodgkin's lymphoma,mixed cell type,stage Ⅳ group B.Chose the chemotherapy regimen BV + GABVD for 4 courses,the PET-CT indicated CR,then used GABVD 4 courses,now in the stage of clinical observation and followed up.Conclusion BV is a kind of antibody-drug conjugate which targeted on CD30 protein.The FDA approved for the treatment of Hodgkin's lymphoma and systemic anaplastic large cell lymphoma.The common adverse reactions are granulocyte,peripheral neuropathy,fatigue,nausea and vomiting.BV can significantly improve the prognosis of CD30 positive Hodgkin's lymphoma,but need to pay attention to the prevention of adverse reactions.
RESUMO
Objective To assess the feasibility of serum soluble CD30 (sCD30) as a biomarker for radiation exposure. Methods Three hundred male C57BL/6 mice were prepared and randomly divided into 4 radiation groups (60 each) and control (n=60). Mice in radiation groups were treated with 60Co total-body irradiation in the dose of 1, 3, 5 or 7 Gy, and the dose rate of 60Co ray at one-time whole-body irradiation was 0.78 Gy/min. 24, 48, or 72h after radiation, the serum samples were obtained (20 mice in each group at each time point). The serum sCD30 concentrations were analyzed with custom-made antibody array, which was purchased from RayBiotech. To further analyze the relationships of serum sCD30 concentration and radiation dose, regression analysis was used. Results The baseline level of sCD30 in serum of non-exposed animals was 121.2±25.61pg/ml. Moreover, serum sCD30 concentration was inversely related to the radiation dose during 72h after exposure. Regression analysis showed an obvious dose-effect relationship between serum sCD30 concentration and radiation dose (24h after radiation, R2=0.8715; 48h after radiation, R2=0.9024; 72h after radiation, R2=0.9913). Using these equations, radiation exposure can be easily estimated by the serum sCD30 value. Conclusions The baseline level of serum sCD30 remains steady without radiation. Further regression analysis uncovers a strong correlation between serum sCD30 concentration and radiation dose, and serum sCD30 may be used to estimate radiation exposure as a biomarker.
RESUMO
Objective To analyze the pre-transplant sera of renal graft recipients for soluble CD30 level and study the correlation between sCD30 level and acute rejection (AR),lung infection or renal graft loss.To investigate the feasibility of sCD30 level for pre-transplant risk evaluation in renal transplant recipients.Methods 586 renal graft recipients were enrolled into this study,who had complete 5-year follow-up data and sufficient pre-transplant sera for analysis.Pre-transplant sera were collected for detection of sCD30 level by ELISA and patients were divided into three groups according to sCD30 level:group L (sCD30＜120 U/ml),group I (sCD30 120-240U/ml) and group H (sCD30 ＞240 U/ml).Incidence of AR,lung infection,graft loss and postoperative 5-year patients and renal allograft survival rate were compared among three groups.Correlation analysis was also performed between pre-operative sCD30 level and postoperative dialysis time,AR,or lung infection.Results The average pre-transplantation sCD30 level was significantly higher than that of healthy individuals (P＜0.01 ).During the 5-year follow-up period,the incidence of AR in groups L,I and H was 17.4％ (45/259),29.2％ (77/264) and 42.9％ (27/63) respectively,and the lung infection rate was 20.8％,8.3％ and 15.9％ respectively.There was significant differences in AR incidence and lung infection rate among these three groups (P＜0.01).The pre-transplantation sCD30 level in patients with AR was (180.0± 89.1) U/ml,which was significantly higher than in those without AR (135.3 ± 72.7 U/ml,P＜0.01).The pre-transplantation sCD30 level in patients with lung infection was (123.2±75.5) U/ml,which was significantly lower than in those without lung infection (150.7 ± 79.6 U/mL,P＜0.01).The pre-transplantation sCD30 level had a positive relationship with AR (r =0.242,P＜0.01),but a negative correlation with lung infection (r=- 0.147,P＜0.01).In group H, five-year cumulative survival rate of recipients and renal grafts was 79.4％ and 69.8％ respectively,which was significantly lower than in group L (90.3％ and 87.3％),and group I (91.3％ and 87.6％) (P＜0.05,P＜0.01),but there was no significant difference between group L and group I (P＜0.01).Conclusion Pretransplant sCD30 level in renal transplant recipients is remarkably correlated with postoperative AR and lung infection,which can be considered as an independent predictor for postoperative AR,lung infection and the risk of graft function loss.
RESUMO
The clinical course of mycosis fungoides is indolent except when large cell transformation occurs. Large cell transformation of MF is rare and easy to misdiagnose. A case of large cell transformation of mycosis fungoides is reported. A 40-year-old man presented with a 10-year history of pruritic erythema and papules in the trunk and extremities as well as a 5-month history of nodules on the nape of the neck.Histopathologically, the erythematous patch showed typical changes of mycosis fungoides, while the tumor cells were small and expressed CD3 and CD4, and only a small number of tumor cells expressed CD30. Pathological examination of nodular lesions revealed the infiltration of large pleomorphic lymphoid cells expressing CD3 and CD4 throughout the entire dermis. There was an epidermotropism of large cells, and about 40% of these cells expressed CD30. Based on the medical history and histological findings, the patient was diagnosed with large cell transformation of mycosis fungoides. The lesions improved markedly after 3-week treatment with oral acitretin (30 mg once daily), subcutaneous interferon-alpha (2 × 106 IU thrice a week) and local superficial X-ray irradiation for nodular lesions. Up to the time of this writing, the patient had been followed.
RESUMO
Objective To clarify clinical and morphological features and immunophenotype and Epstain-Barr virus infection of neoplastic cell rich Hodgkin's lymphoma (NCRHL)and to further improve our knowledge and pathological diagnosis for NCRHL. Methods 10 cases of NCRHL were analyzed for clinical features, morphology, immunophenotype, Epstein-Barr virus infection using routine eosin and haematoxylin stain, immunohistochemistry, Epstain-Barr virus encoded small RNA (EBER) in situ hybridization and combining clinical data. Results (1)NCRHL were more common in young people. The median age of the patients was 25.5 years old. The ratio of male to female was 1:2.3. Superficial lymph nodes were most frequently involved. Masses of mediastinum were seen commonly. Clinical manifestation of the patients included B symptom (6 cases), pruitus (5 cases) and anemia (1 case). (2)Architecture of lymph nodes were effected. Necrosis was seen in some cases. There were more tumor cells in NCRHL than that in the classical Hodgkin's lymphoma. The tumor cells were distributed in piece or patch or diffuse. The morphology of neoplastic cells was wore variable including Hodgkin-like cells, lacunar cell-like, mummy cell-like and anaplastic large cell-like, singular nucleated cells, and multinucleated giant cell-like cells. Numerous neutrophils and eosinophils were present in a few cases. Focal sheet, necrosis granulomatosis-like and diffuse growth pattern were found in NCRHL. (3)All of the cases were positive for CD30 and PAX-5.2/10 (20%) cases were CD15 positive. LCA, CD20 and CD3 were negative. (4)EBER was not detected in all 6 tested cases. (5)Follow up data was obtained in 8/10 cases, in which one patient was dead, one case relapsed in half a year,and the other 6 cases reached complete regression. Conclusion NRCHL is characterized mainly by neoplastic cell rich morphologically and focal sheet, necrosis granulomatosis-like and diffuse growth pattern.EBER was not detected in this tumor. Some cases have aggressive clinic process with a unfavourable prognosis. New treatment regimen should be explored.
RESUMO
Objective To approach the expression and significance of CD30 in Hodgkin lymphoma cells which were transfected with mtr Ⅱ gene. Methods The CD30 expression of Hodgkin lymphoma cells in those transfected with mtr Ⅱ gene was analysed by immunohistochemical technique respectively. Results The CD30 expression rate of Hodgkin lymphoma cells which were transfected with mtr Ⅱ gene was higher than that of Hodgkin lymphoma cells which weren't transfected with mtrⅡ gene (P ＜0.01). Conclusion The mtr Ⅱ gene may be related to the malignant transformation of Hodgkin lymphoma.
RESUMO
Gastric CD30-positive anaplastic large-cell lymphoma is a very rare disease. It is sometimes difficult to distinguish it from undifferentiated carcinoma, sarcoma and so on. We report here on a case of primary gastric anaplastic large-cell lymphoma. A 50-yr-old woman complained of epigastric pain and severe chest pain for 1 week. The gastroendoscopic examination revealed geographic mucosal irregularities with shallow ulceration at the antrum. She underwent a total gastrectomy. The gross finding of the resected stomach was an 8 x 4.5 cm sized ulceroinfiltrative lesion at the pyloric antrum along the lesser curvature. The microscopic examination revealed diffuse and solid proliferations of large atypical cells with pleomorphic nuclei. Immunohistochemically, the tumor cells were positive for CD30, vimentin and CD3, and this was a finding compatible with anaplastic large-cell lymphoma. To the best of our knowledge, this is the first such reported case in Korea.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Antígeno Ki-1/metabolismo , Imuno-Histoquímica , Coreia (Geográfico) , Linfoma Difuso de Grandes Células B/enzimologia , Proteínas Tirosina Quinases/metabolismo , Neoplasias Gástricas/enzimologiaRESUMO
The incidence of posttransplantation lymphoproliferative disorders (PTLDs) has increased in recent years. Although rare, various types of T-cell lymphoma have been reported and their association with Epstein-Barr virus (EBV) has been compared with B-cell PTLDs. We report a case of splenic peripheral T-cell lymphoma occurring in a 47-yr-old male patient 7 yr after renal allograft transplantation. The spleen showed sinusoidal proliferation of focal CD30 positive, large, atypical lymphoid cells. Positivity for CD3 and cytolytic granule-associated proteins was also demonstrated in the tumor cells, while anaplastic large cell lymphoma kinase (ALK) and CD8 were not expressed. Strong nuclear signals for EBV mRNA were noted by EBER1 in situ hybridization. A molecular genetic study demonstrated a rearrangement of the gamma T-cell receptor gene. To our knowledge, this case is unique in terms of a posttransplant T-cell lymphoma that shows focal CD30, cytolytic granule-associated proteins, and EBV positivity.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Ki-1/genética , Antígeno Ki-1/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Transplante de Rim , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/virologia , Proteínas de Membrana/metabolismo , RNA Viral , Proteínas de Ligação a RNA/metabolismo , Serina Endopeptidases/metabolismo , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/virologiaRESUMO
AIM: To investigate the details of Th2 cell differentiation in septic mice. METHODS: Experimental septic mice were induced by cecal ligation and puncture (CLP). The exression of CD30 on CD4 +T cells at different time after CLP were estimated by flow cytometry following three-color immunofluorescent staining.RESULTS: CD30 expression on CD4 +T cell was different at each time point. The highest expression was showed at 38 h after CLP and declined later, which matched the changes in mortality of the animals. CONCLUSION: During sepsis, differentiation of Th2 cell changed with the development of sepsis and might be associated with the severity of the disease.
RESUMO
To observe the state of balance between Th1/Th2 in children with asthma by assaying lymphocyte produced cytokines and the expression of CD30 membrane antigen on PBMC. The levels of IFN ?, IL 4 in PBMC and serum total IgE were determined by ELISA, the counting of the CD30 expressing cells was performed by flow cytometry. The results showed: (1)The level of IL 4 was increased significantly in patients with asthma attack compared with normal children ( P