镇肝熄风汤对自发性高血压大鼠视网膜细胞保护作用机制的研究

目的:探索镇肝熄风汤对自发性高血压大鼠视网膜细胞的保护作用机制。方法:将48只SHR随机分为4组:模型组(B)、贝那普利对照组(C)、镇肝熄风汤低剂量观察组(D)、镇肝熄风汤高剂量观察组(E);每组各12只。正常空白组WKY(A)12只。镇肝熄风汤低剂量组灌服镇肝熄风汤15g·kg^(-1)·d^(-1)(药物浓度1.5g/m L);镇肝熄风汤高剂量组灌服镇肝熄风汤30g·kg^(-1)·d^(-1)(药物浓度3.0g/m L);贝那普利组灌服贝那普利0.90mg·kg^(-1)·d^(-1)。模型组(B)及WKY组每日灌服同体积的蒸馏水。共8周。检测干预前后大鼠血压,免疫组织化学法检测Bcl-2、Bax的表达。结果:干预前与空白组(WKY大鼠)比较,其他各组(SHR大鼠)收缩压、舒张压和平均血压明显高于同周龄的WKY大鼠(P<0.05);各组大鼠干预8周后再次进行血压测定,与模型组比较,各治疗组收缩压、舒张压和平均血压显著降低(P<0.05);镇肝熄风汤减轻了SHR的Bax表达(P<0.01),增加了Bcl-2的表达,其中中药高剂量组达到WKY水平(P>0.05)。结论:镇肝熄风汤不仅有明显的降压作用,而且在高血压病程中可抑制视网膜毛细血管的细胞凋亡。

Gastric infiltration of diffuse large B-cell lymphoma: Endoscopic diagnosis and improvement of lesions after chemotherapy

Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of the non-Hodgkin’s lymphoma (NHL) accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-mo history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy (CT) scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.

Preliminary outcome of rituximab-containing salvage regimens on relapsed or refractory B-cell non-Hodgkin’s lymphoma: single institution experience

Objective： The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy, Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease free survival （DFS） and overall survival （OS） of naive patients, but its role in the second-line therapy for relapsed non-Hodgkin＇s Lymphoma （NHL） remains to be defined, This study aimed to evaluate the efficacy of rituximab-containing salvage regimens for relapsed or refractory NHL, and observe the toxicities. Methods： The clinical data of 54 patients, who were with relapsed or refractory NHL and treated in the Cancer Center of Sun Yat-sen University, were analyzed retrospectively, Of the 54 patients, 29 were man, 25 were women, with a median age of 52.5 years old （range 18 to 75）; 50 patients （92.6%） scored 0-1 for the ECOG performance status; for second-line international prognostic index （slPI）, 21 （38.9%） scored 0-1,30 （55.6%） scored 2 to 3, and 3 （5.6%） scored 4-5; 40 cases were diffuse large B-cell lymphoma （DLBCL）, accounting for 74.1% of all subtypes, Rituximab was administered intravenously at a dose of 375 mg/m^2 at the day before each chemotherapy cycle, The second or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16 and FND, Results： Of the 54 patients, 49 received retuximab-containing salvage regimens, The objective response rate of the 45 evaluable cases was 68,8%, with a complete remission （CR） rate of 37.7%; 3 patients achieved CR after radiotherapy following rituximab-based regimens and 3 achieved CR after autologous hematopoietic stem cell transplantation, The most frequent adverse events were leucopenia, nausea and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever and pruritus. The median follow-up time was 18 months （range 2-86 months）; 5 patients were lost, 24 were dead （23 died of lymphoma, and 1 died of severe hepatitis）, the other patients remained alive. The median survival time was 32 months （range 2-86 months, 95% confidential interval 16-48 months）. The 1-, 2- and 3-year OS rates were 70.6%, 53,6% and 41,5%, respectively, The median TTP was 6 months （range 0-52 months）, The median PFS was 10 months （range 0-47 months, 95% CI 0-26 months）, The 1- and 2-year PFS were 49,3% and 41,3%. Conclusion： Rituximab-containing salvage regimens are effective and well tolerated therapy for patients with relapsed or refractory B-cell NHL, even those were extensively treated.

The gene expression patterns of BMPR2,EP300,TGFβ2,and TNFAIP3 in B-Lymphoma cells

Objective: The results of a previous study showed that a clear dysregulation was evident in the global gene expression of the BCL11A-suppressed B-lymphoma cells. In this study, the bone morphogenetic protein receptor, type II(BMPR2), E1 A binding protein p300(EP300), transforming growth factor-β2(TGFβ2), and tumor necrosis factor, and alpha-induced protein 3(TNFAIP3) gene expression patterns in B-cell malignancies were studied. Methods: The relative expression levels of BMPR2, EP300, TGFβ2, and TNFAIP3 mRNA in B-lymphoma cell lines, myeloid cell lines, as well as in cells from healthy volunteers, were determined by real-time quantitative reverse transcriptpolymerase chain reaction(qRT-PCR) with SYBR Green Dye. Glyceraldehyde-3-phosphate dehydrogenase(GAPDH) was used as reference. Results: The expression level of TGFβ2 mRNA in B-lymphoma cell lines was significantly higher than those in the cells from the healthy control(P<0.05). However, the expression level of TNFAIP3 mRNA in B-malignant cells was significantly lower than that of the healthy control(P<0.05). The expression levels of BMPR2 and EP300 mRNA showed no significant difference between B-malignant cell lines and the healthy group(P>0.05). In B-lymphoma cell lines, correlation analyses revealed that the expression of BMPR2 and TNFAIP3(r=0.882, P=0.04) had significant positive relation. The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in cell lines from myeloid leukemia were significantly lower than those in the cells from the healthy control(P<0.05). The expression levels of TGFβ2 mRNA showed no significant difference between myeloid leukemia cell lines and the healthy control or B-malignant cell lines(P>0.05). The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in B-lymphoma cells were significantly higher than those of the myeloid leukemia cells(P<0.05).Conclusion: Different expression patterns of BMPR2, EP300, TGFβ2, and TNFAIP3 genes in B-lymphoma cells exist.

Expression profile of CD10, Bcl-6, CD138, Bcl-2 and MUM1 and their prognostic value in 136 patients with diffuse large B-cell lymphoma

Objective： We evaluated the value of using a panel of GC B-cell （CD10 and Bcl-6） and activation （MUM1, CD138 and Bcl-2） markers by immunohistochemistry to define prognosis in patients with diffuse large B-cell lymphoma （DLBCL）. Methods： Two different models （Hans＇ and modified Chang＇s model） were applied on 136 de hove DLBCL patients. Median follow-up in all patients was 39 months （range 5-80 months）. Results： According to Hans＇ model, patients with GCB had much better overall survival （5-year OS, 75%） than those with non-GCB （5-year OS, 52%） （Kaplan-Meier survival analysis, P 〈 0.05, log rank test）. According to modified Chang＇s model, patients with group 1 had much better overall survival （5-year OS, 78%） than those with group 3 （5-year OS, 44%） while group 2 had no significant value compared with group 1 and group 3 in prognosis （Kaplan-Meier survival analysis, P 〈 0.05, log-rank test）. Using multivariate Cox proportional hazards regression analysis, the international prognostic index scores （IPI）, expression of CD138 and the expression pattern of modified Chang＇s model were independent prognostic indicators. Conclusion： Our results suggest that the expression patterns of the panel of GCB-cell and activation markers by immunohistochemistry correlate with prognosis of patients with DLBCL and both models can be used well in ordinary work.

Lidamycin Induces Apoptosis of B-Cell Lymphoma Cells and Inhibits Xenograft Growth in Nude Mice

OBJECTIVE To study the cytotoxicity of Lidamycin （LDM） and its induction of apoptosis in Raji and Daudi cells of B-cell lymphoma, and the inhibition of growth of the lymphoma Raji xenograft in nude mice. METHODS MTT assay was used to observe the inhibition by LDM on the proliferation of the Raji and Daudi ceils. Annexin V-FITC/PI double-stain, in combination with flow cytometry （FCM）, was used to determine the induction of apoptosis by LDM in Raji cells. The B-cell lymphoma Raji xenograft model in nude mice was set up to detect the in vivo antitumor activity of LDM. RESULTS LDM markedly inhibited the proliferation of the Raji and Daudi cells in vitro, with IC50 values of 7.13×10^-11 mol/L and 2.91×10^-10 mol/L, respectively. The apoptotic rates of Raji cells were respectively 77.98% and 67.63% at 0.5 nmol/L and 0.25 nmol/L of LDM, indicating an obvious induction of apoptosis in Raji cells. LDM inhibited the formation and growth of human B-cell lymphoma Raji xenograft in nude mice. The inhibition rates of tumor growth were respectively 74.9% and 65.2% in LDM at dosage group of 0.05 mg/kg and 0.025 mg/kg, suggesting an apparent prolongation of survival time in the nude mouse bearing lymphoma. CONCLUSION LDM can effectively induce apoptosis of the B-cell lymphoma cells and inhibit the xenograft growth in nude mice.

Primary lymphoblastic B-cell lymphoma of the stomach:A case report

Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo. Gastrofiberscopy revealed a large gastric ulcer, which was successfully resected. Pathology showed a lymphoblastic cell lymphoma arising from the stomach, and there was no evidence of disease at any extrastomach site. Immunohistochemical staining and gene rearrangement studies supported that the stomach tumor was a clonal B-cell lymphoma. Therefore, the diagnosis of B-LBL was made based on the stomach specimen.

Expression of the B-Cell Lymphoma/Leukemia 11A Gene in Malignant Hematological Cell Lines through Quantitative Reverse Transcription Polymerase Chain Reaction

The B-cell lymphoma/leukemia 11A （BCL11A） gene is essential for normal lymphoid development and has been associated with hematological malignancies. In the current study, the relative expression level of BCL11A in malignant hematological cell lines was evaluated through real-time quantitative reverse transcription polymerase chain reaction （qRT-PCR）. METHODS The relative expression level of BCLllA mRNA in malignant hematological cell lines was determined through qRT- PCR using SYBR Green I dye. Glyceraldehyde-3-phosphate dehydro- genase was used as the reference gene to confirm the relative expression level of BCL11A gene mRNA. RESULTS The relative expression level of BCL11A mRNA in cell lines from B-cell malignancies was significantly higher compared with that from acute rnyeloid leukemia （P 〈 0.05）. Different cell lines with malignant B-cells exhibited a wide range of BCL11A expressions ranging from 27.37 to 93.38. CONCLUSION The overexpression of BCL11A gene mRNA in malignant B-cells might play a role in B-cell lymphoma/leukemia.

Significance of stromal-1 and stromal-2 signatures and biologic prognostic model in diffuse large B-cell lymphoma

Objective:Diffuse Large B Cell Lymphoma(DLBCL)is a heterogeneous group of tumors with different biological and clinical characteristics that have diverse clinical outcomes and response to therapy.Stromal-1 signature of tumor microenvironment of DLBCL represents extracellular matrix deposition and histiocytic infiltrate,whereas stromal-2 represents angiogenesis that could affect tumor progression.Methods:The aim of the present study is to assess the significance of stromal-1 signature using SPARC-1 and stromal-2 signature using CD31 expression and then finally to construct biologic prognostic model(BPM)in 60 cases of DLBCL via immunohistochemistry.Results:Microvessel density(P<0.05)and SPARC percentage of expression(P<0.001)were higher in DLBCL,including germinal and nongerminal cases,compared with reactive follicular hyperplasia.High microvessel density was significantly associated with splenic involvement(P=0.008),high mitotic count(P=0.045),and presence of capsular invasion(P=0.035).Percentage of SPARC expression was significantly associated with splenic involvement(P=0.03).Constructing BPM showed that 42 cases(70%)were of low biologic score(0–1)and 18 cases(30%)were of high biologic score(2–3).Low BPM cases showed less probability for splenic involvement(P=0.04)and a higher rate of complete response to therapy compared with high score cases(P=0.08).Conclusions:The DLBCL microenvironment could modulate tumor progression behavior since angiogenesis and SPARC positive stromal cells promote dissemination by association with spleen involvement and capsular invasion.Biologic prognostic models,including modified BPM,which considered cell origin of DLBCL and stromal signature pathways,could determine DLBCL progression and response to therapy.

Rituximab in Combination with CHOP, an Effective and Well-tolerated Salvage Regimen for Diffuse Large B-Cell Lymphoma

OBJECTIVE To evaluate the clinical effect of the R-CHOP regimen (rituximab in combination with cyclophosphamide, epirubicin, vincristine and prednisone) in treating refractory or relapsed diffuse large B-cell lymphoma (DLBCL), as a salvage therapy for DLBCL. METHODS Eighteen patients with refractory or relapsed DLBCL who were treated with the R-CHOP regimen from 2001 to 2006 in hospitals in Jilin Province were analyzed retrospectively. The response rate, change of serum lactate dehydrogenase (LDH), time to progression (TTP) and toxicity were observed. RESULTS The R-CHOP regimen can achieve a higher response rate, decrease serum LDH to a larger extent and obtain longer TTP than a con- ventional secondary regimen. The main adverse effects were similar to con- ventional chemotherapy. CONCLUSION The R-CHOP regimen is one of the most effective sec- ondary therapies for DLBCL.

Construction and analysis of tree models for chromosomal classification of diffuse large B-cell lymphomas

AIM: To construct tree models for classification of diffuse large B-cell lymphomas (DLBCL) by chromosome copy numbers, to compare them with cDNA microarray classification, and to explore models of multi-gene, multi-step and multi-pathway processes of DLBCL tumorigenesis. METHODS: Maximum-weight branching and distancebased models were constructed based on the comparative genomic hybridization (CGH) data of 123 DLBCL samples using the established methods and software of Desper et al . A maximum likelihood tree model was also used to analyze the data. By comparing with the results reported in literature, values of tree models in the classification of DLBCL were elucidated. RESULTS: Both the branching and the distance-based trees classified DLBCL into three groups. We combined the classification methods of the two models and classified DLBCL into three categories according to their characteristics. The first group was marked by +Xq, +Xp, -17p and +13q; the second group by +3q, +18q and +18p; and the third group was marked by -6q and +6p. This chromosomal classification was consistent with cDNA classification. It indicated that -6q and +3q were two main events in the tumorigenesis of lymphoma. CONCLUSION: Tree models of lymphoma established from CGH data can be used in the classification of DLBCL. These models can suggest multi-gene, multistep and multi-pathway processes of tumorigenesis. Two pathways, -6q preceding +6q and +3q preceding+18q, may be important in understanding tumorigenesis of DLBCL. The pathway, -6q preceding +6q, may have a close relationship with the tumorigenesis of non-GCB DLBCL.

Gastric Diffuse Large B-Cell Lymphoma after the Diagnosis of Primary MALT Lymphoma of the Breast One Case Report

Primary breast and gastric lymphomas as manifesta-tions of primary extranodal lymphomas are rare malignancies, and their diagnosis, prognosis, and treatment modalities remain unclear. We report for the first time the simultaneous co-occurrence of these diseases in one patient. A 60-year-old woman was diagnosed with gastric diffuse large B-cell lymphoma （DLBCL） 2.5 years after she was found to have primary mucosa-associated lymphoid tissue （MALT） lymphoma of the breast. Although the patient underwent che-motherapy, she died of leukemia that caused irreversible cytopenia of three lineages. The data show that her MALT lymphoma apparently transfigured into gastric DLBCL. This case highlights the importance of evaluating patients for Helicobacter pylori infection when they present with extranodal MALT lymphomas, except gastric ones. Positive test findings should prompt anti-H, pylori therapy to prevent MALT lymphomas from transforming into DLBCLs.

Diffuse large B-cell lymphoma of cerebellum five months after left atrial myxoma resection in an old woman

We describe a 70-year-old female patient with diffuse large B-cell lymphoma of the cerebellum;she received resection of a left atrial myxoma five months ago.To the best of our knowledge,to date no association of atrial myxoma with the malignant cerebellar diffuse large B-cell lymphoma has been reported in the literature,except for high level of interleukin-6 (IL-6) in the serum under both conditions.IL-6 as a pro-inflammatory cytokine has been shown to be associated with tumor progression,including inhibition of cancer cell apoptosis and stimulation of angiogenesis.IL-6 concentrations may provide possible aetiological links between atrial myxoma and cerebellar diffuse large B-cell lymphoma in our case.

CHOP-like Regimen in Combination with Rituximab and Peginterferon Alpha-2b in Newly-diagnosed Diffuse Large B-cell Non-Hodgkin＇s Lymphoma： Experience in a Chinese Center

OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin＇s lymphoma （DLBCL）.METHODS From January 2003 to July 2008, 51 patients received CHOP-like chemotherapy （cyclophosphamide 750 mg/m2, epirubicin 80 mg/m2, vindesine 2.8 mg/m2 on day 1, and prednisolone 100 mg/day on day 1 to day 5）. Thirty-one patients received CHOPR-like treatment （rituximab 375 mg/m2 1 day before CHOP-like chemotherapy）. Twenty patients received CHOP-like regimen in combination with peginterferon （pegIFN） （1μg/kg on day 5） and rituximab （on day 6）.RESULTS -The CR （complete remission） rate in the CHOPR-like （with or without pegIFN） group and in the CHOP-like group was 78.4% and 45.1% （P = 0.005）, respectively. The estimated mean time of overall survival （OS） in the CHOPR-like group and CHOP- like group was 58.7 ± 2.8 and 36.4 ±3.4 months, respectively （P = 0.002）. The rates of CR and OR （overall remission） in CHOPR- like with IFN arm were 85.0% and 95.0%, and the rates of those in CHOPR-like without IFN arm were 74.2% and 87.0% （P 〉 0.05）. The estimated mean time of 4-year-PFS （progression- free survival） in CHOPR-like with IFN arm and in CHOPR-like without IFN arm was 62.9 ±3.0 months and 51.0 ± 4.6 months （P = 0.092）, respectively. In the CHOPR-like with IFN arm, no patient relapsed after achieving CR, while the estimated rate of 4-year- DFS （disease-free survival） in the patients who reached CR in the CHOPR-like without IFN arm was （63.4 ± 19.3）% （P = 0.061）. CONCLUSION Rituximab combined with CHOP-like chemotherapy improved the prognosis of DLBCL patients. The IFN may help to improve the quality and duration of response of DLBCL patients treated with rituximab and CHOP-like regimen.

Retrospective analysis of hepatitis B virus reactivation after rituximab combination chemotherapy in patients with B-cell lymphoma

Objective： The aim of the study was to investigate the reactivations of hepatitis B virus （HBV） after rituximab- containing chemotherapy in patients with B-cell lymphoma with surface antigen of hepatitis B virus （HBsAg）-positive, or hepatitis B core antibody （HBcAb）-positive. Methods： A retrospective study of HBV-related markers was performed before and after dtuximab-containing treatment in 189 consecutive patients with CD20-positive B-cell lymphoma. Results： Among the 189 non-Hodgkin＇s lymphoma （NHL） patients who received rituximab combination chemotherapy, 31 （16.6%） were HBsAg positive and 82 （43.9%） HBsAg negative/HBcAb positive, and 76 were HBsAg and HBcAb negative. Of the 31 HBsAg positive patients, 3 （9.7%） experienced reactivation of HBV. The prevalence of HBV reactivation was 4.0% （1/25） in patients who received prophylactic antiviral treatment and 33.3% （2/6） in those who did not receive prophylactic antiviral treatment （P = 0.032）. Prophylactic antiviral treatment decreased the rate of HBV reactivation. Among the 82 HBsAg negative/HBcAb positive patients, 1 （1.2%） experienced HBV reactivation leading to serious hepatitis. Conclusion： Our experience indicates that rituximab-based therapy may cause serious HBV-related complications and even death in HBsAg-positive patients. Preemp- tive use of antiviral treatment enabled successful management of HBV reactivation. In HBsAg-negative and HBcAb-positive lymphoma patients the prevalence of HBV reactivation is low （1.2%）. Close monitoring HBV until at least 6 months after anticancer therapy is required, prophylactic antiviral therapy needs to be evaluated further.

Observation of the Curative Effect of Mabthera in Combination with the CHOP Regimen in Treating Invasive B-Cell Lymphoma:A Report of 45 Cases

OBJECTIVE To observe the clinical efficacy and toxic effects of Mabthera （rituximab） in combination with the CHOP （R-CHOP） regimen for treating invasive B-cell non-Hodgkin＇s lymphoma. METHODS A total of 45 patients with CD20 positive B-cell non- Hodgkin＇s lymphoma were randomly divided into the R-CHOP （22 cases） and CHOP groups （23 cases for controls）. They received the regimens of Mabthera in combination with CHOP or single CHOP therapy respectively. An appraisement of the curative effect could only be performed following 4 cycles of chemotherapy for the 45 patients. Follow-up was conducted to observe the conditions of survival. RESULTS The rate of complete remission （CR） in the R-CHOP group was 68.2%, with a total effective rate of 81.8%, and in the CHOP group these rates were 34.8% and 78.3% respectively. There was a significant difference in comparing the CR rates between the two groups （P 〈 0.05）. The 1, 2 and 3-year overall survival （OS） rates of the RCHOP group were 90.9%, 81.8% and 77.3%, respectively. In the CHOP group, the OS rates were respectively 91.3%, 69.5% and 47.8%. The difference in the 3-year OS between the two groups was significant （P 〈 0.05）. The toxic effects of the two groups were mainly a slight and moderate bone marrow depression and a gastrointesinal reaction, with similar tolerable toxic effects in the two groups （P 〉 0.05）. Adverse effects related to the Mabthera infusions occurred in 6 cases of the R-CHOP group （27.2%）. These effects lessened after symptomatic treatment. CONCLUSION The therapeutic regimen of Mabthera, in combination with CHOP （R-CHOP） has an obvious curative effect for treating invasive B-cell non-Hodgkin＇s lymphoma, with a favorable tolerance. It is highly recommended as the treatment of choice.

PCNA、BCL-2和P53^(mt)蛋白在燃煤型砷中毒患者不同病变皮肤中的表达及相关性分析

目的 分析燃煤型砷中毒患者皮肤癌变过程中增殖细胞核抗原 (PCNA)、B-淋巴细胞瘤 /白血病 - 2抗凋亡蛋白 (BCL- 2 )和突变型 P5 3基因蛋白 (P5 3mt)的表达情况及相关性。方法 免疫组化 ABC法和En Vision TM +System两步法。结果 PCNA、BCL- 2和 P5 3mt蛋白在砷中毒患者的不同病变皮肤中均有表达 ,且无论是阳性细胞密度还是阳性率均呈现出癌变组 (A组 ) >癌前组 (B组 ) >一般病变组 (C组 )的趋势 ;癌变组 3项指标协同阳性率为 83.33% ,明显高于癌前组的 5 4.5 4%和一般病变组的 2 3.0 8% ;任何两指标间均有高度相关性(P<0 .0 1)。结论 PCNA、BCL- 2和 P5 3mt的协同高表达是砷性皮肤病变恶性转化的重要标志 ,皮肤角化过度患者有相当比例的表达 ,提示其具有恶变的潜在危险 ;燃煤型砷中毒致皮肤癌变过程中 ,PCNA、BCL - 2和 P5

燃煤型砷中毒患者不同病变皮肤的分子病理学研究

目的探索燃煤型砷中毒患者皮肤良恶性病变的增殖细胞核抗原(PCNA)、B-淋巴细胞瘤／Ca血病-2抗凋亡蛋白(BCL-2)和突变型P53基因蛋白(P53^mt)的表达及其病理生物学意义。方法采用免疫组化ABC法和EnVision+System两步法并结合组织病理学观察。结果PCNA，BCL-2和P53^mt蛋白在砷中毒患者的不同病变皮肤中均有表达，且无论是阳性细胞密度还是阳性率均呈现出癌变组(A组)>癌前组(B组)>一般病变组(C组)的趋势，癌变组三指标协同阳性率为83．33％，明显高于癌前组的54．54％和一般病变组的23．08％，癌变组及癌前组与一般病变组间的差异均有显著性(P<0．01和P<0．05)；任何两指标间均有高度相关性(P<0．01)。结论(1)PCINA、UCL-2和P53“的协同高表达是砷性皮肤病变恶性转化的重要标志，皮肤角化过度患者有相当比例的表达，提示其具有恶变的潜在危险；(2)燃煤型砷中毒致皮肤癌变过程中，细胞增殖、P53^mt基因突变及抗凋亡增强协同起作用，PCNA、BCL-2和P53^mt的异常表达可对砷致皮肤癌的癌前监控和预测提供重要佐证。

Generation and selection of immunized Fab phage display library against human B cell lymphoma

The approval of using monoclonal antibodies as a targeted therapy in the management of patients with B cell lymphoma has led to new treatment options for this group of patients. Production ofmonoclonal antibodies by the traditional hybridoma technology is costly, and the resulting murine antibodies often have the disadvantage of triggering human anti-mouse antibody （HAMA） response. Therefore recombinant Fab antibodies generated by the phage display technology can be a suitable alternative in managing B cell lymphoma. In this study, we extracted total RNA from spleen cells of BALB/c mice immunized with human B lymphoma cells, and used RT-PCR to amplify cDNAs coding for the κ light chains and Fd fragments of heavy chains. After appropriate restriction digests, these cDNA fragments were successively inserted into the phagemid vector pComb3H-SS to construct an immunized Fab phage display library. The diversity of the constructed library was approximately 1.94× 10^7. Following five rounds of biopanning, soluble Fab antibodies were produced from positive clones identified by ELISA. From eight positive clones, FabC06, FabC21, FabC43 and FabC59 were selected for sequence analysis. At the level of amino acid sequences, the variable heavy domains （VH） and variable light domains （VL） were found to share 88-92% and 89-94% homology with sequences coded by the corresponding murine germline genes respectively. Furthermore, reactivity with membrane proteins of the B cell lymphoma was demonstrated by immunohistochemistry and western blotting. These immunized Fab antibodies may provide a valuable tool for further study of B cell lymphoma and could also contribute to the improvement of disease therapy.

Primary gastrointestinal lymphoma

Gastrointestinal tract is the most common extranodal site involved by lymphoma with the majority being non-Hodgkin type.Although lymphoma can involve any part of the gastrointestinal tract,the most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region.Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare.Gastrointestinal lymphomas are usually not clinically specific and indistinguishable from other benign and malignant conditions.Diffuse large B-cell lymphoma is the most common pathological type of gastrointestinal lymphoma in essentially all sites of the gastrointestinal tract,although recently the frequency of other forms has also increased in certain regions of the world.Although some radiological features such as bulky lymph nodes and maintenance of fat plane are more suggestive of lymphoma,they are not specific,thus mandating histopathological analysis for its definitive diagnosis.There has been a tremendous leap in the diagnosis,staging and management of gastrointestinal lymphoma in the last two decades attributed to a better insight into its etiology and molecular aspect as well as the knowledge about its critical signaling pathways.