PD0325901, an ERK inhibitor, enhances the efficacy of PD-1 inhibitor in non-small cell lung carcinoma

ERK pathway regulated the programmed death ligand-1 (PD-L1) expression which was linked to the response of programmed death-1 (PD-1)/PD-L1 blockade therapy. So it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer immunotherapy. In this study, PD0325901, an oral potent ERK inhibitor, strongly enhanced the efficacy of PD-1 antibody

Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

Analysis of molecular characteristics and prognosis in acute myeloid leukemia patients with AML1/ETO / 白血病·淋巴瘤

Objective To analyze the molecular characteristics and prognosis in acute myeloid leukemia patients with AML1/ETO.Methods The clinical data of 63 cases of acute myeloid leukemia (AML) patients with AML1/ETO positive were analyzed retrospectively.56 cases of AML patients with AML1/ETO negative in the same period were analyzed as control.Characteristics in morphology,immunology,cytogenetics,molecular biology and the clinical effects of treatment were studied and analyzed.Results M2a was 57.12 ％ (36/63),M2b was 33.33 ％ (21/63) in AML with AML1/ETO.The percent of initial marrow blasts was 0.46±0.16.The positive rate of CD34,CD13,CD33,CD19,CD7 and CD56 was 67.21％,52.46 ％,40.98 ％,63.93 ％,4.92 ％ and 50.82 ％,respectively.The rate of t(8;21) translocation was 82.54 ％.There was 4.76 ％ with additional chromosome abnormality,three cases with EV1 1and one case with MLL/AT9.The overall CR rate,the relapse rate,the 3-year and the 5-year overall survival rate was 71.43 ％,51.11％,(43.01±5.31) ％ and (32.79±3.81) ％,respectively.There was no significant difference compared with the control group (P ＞ 0.05).But extramedullary infiltration,the expression of CD56 and additional chromosome abnormality had statistical effects on overall survival (P ＜ 0.05).Conclusions There has unique characteristics in AML with AML1/ETO.The effects of treatment and the prognosis are affected by many factors,so the efficacy and prognosis of AML with AML1/ETO couldn' t just depend on AML1/ETO.

Effect of human telomerase reverse transcriptase C27 polypeptide over-expression on growth of transplanted nasopharyngeal carcinoma in nude mice / 肿瘤研究与临床

Objective To investigate the effect of human telomerase reverse transcriptase C27 polypeptide (hTERTC27) over-expression on orthotopic implanted tumor growth which induced by nasopharyngeal carcinoma cells C666-1 in vivo.Methods Stably transfected C666-1 cell lines were used to establish subcutaneously transplanted tumor mouse model.The tumor growth was observed and the tumor growth curve was made by measuring the volumes of tumors every day.HE staining was used to observe the change of histomorphology.The expressions of cleaved Caspase-3,Caspase-9,PARP,bax and bcl-2 were detected by Western blot analysis.Results The in vivo mouse model showed that over-expression of hTERTC27 significantly reduced tumor volume and tumor weight (P ＜ 0.05),and decreased the local muscle infiltration.Over-expression of hTERTC27 significantly up-regulated the expressions of cleaved Caspase-3,Caspase-9,PARP and bax (P ＜ 0.01),and down-regulated the expression of bcl-2 (P ＜ 0.01).Conclusion The results indicate that over-expression of hTERTC27 can obviously inhibit the growth of transplanted tumor in nude mice,which is possibly related to the regulation of bax and bcl-2 expression.

Hospital infection and its risk factors in elderly acute leukemia patients with multifactor logistic-regression analysis / 白血病·淋巴瘤

Objective To investigate the characteristics and risk factors of hospital infection in elderly patients with acute leukemia and provide basis for its prevention and treatment. Methods The hospital infection rate,infection sites,pathogenic bacteria and infectious factors of 116 elderly patients with acute leukemia between January 1999 and January 2008 were analyzed retrospectively,and compared with groups of non-elderly patients in the corresponding period. Results The incidence of hospital infection [62.9 %(73/116)]and death[52.1 %(38/116)]in elderly patients were higher than that of non-elderly ones (P <0.01). The most commonly infective sites were oral cavity and respiratory system. The multiple and serious infection in elderly patients was more than that of non-elderly noes. The common pathogenic bacteria were mainly grant-negative one. The results of multivariate aralysis showed that the absolute neutrophil count in peripheral blood,cycles of chemotherapy,latest infections,stages of treatment,length of hospitalization and seasons on hospitalization were found as independent risk factors for hospital infection in elderly patients with acute leukemia. Conclusion The incidence of hospital infection and death in elderly patients was high. The absolute neutrophil count in peripheral blood,cycles of chemotherapy,latest infections,stages of treatment,length of hospitalization and seasons on hospitalization are independent risk factors for elderly patients with acute leukemia.

Role of radiotherapy in the combined treatment of patients with early stage extranodal nasal type NK/T-cell lymphoma and analysis of prognostic factors / 中华放射肿瘤学杂志

Objective To investigate the role of radiotherapy (RT) and prognostic factors in the combined modality treatment (CMT) of patients with stage ⅠE-ⅡE extranodal nasal type NK/T-cell lym-phoma. Methods From Dec. 1990 to Dec. 2006,177 patients who were diagnosed and treated in our hos-pital were retrospectively analyzed,induding 37 received chemotherapy (CT) alone ( median 4 cycles), 128 received CT (median 3 cycles) followed by RT (median 52 Gy) ,6 received RT alone (median 58 Gy) and 6 received RT ( median 54 Gy) followed by CT ( median 5 cycles). Results The overall response ( CR + PR) rate after initial CT was 60.8% compared with 83.8% after RT ( x2 = 28.63, P < 0.01 ). The 5-year overall survival (OS) and progress-free survival (PFS) rates were 46.2% and 36.8% ,respectively. The lo-cal control rates were 80.9% for RT ( alone or with CMT) and 50.0% for CT alone (x2 = 14.39, P < 0.01 ), and corresponding 5-year OS and PFS were 53.4% vs. 18.3 % ( x2 = 23.38, P < 0.01 ) and 45.0% vs. 10.9% (x2 =23.46,P <0.01 ),respectively. Compared with CT alone,the following definitive RT for patients who achieved response or not after initial CT significantly improved the local control [83.5%, 76.2% vs. 50.0% (x2 = 14.13,P <0.01;x2 =5.78,P <0.01)] and 5-year OS[56.2%,48.6% vs. 18.3%(x2 =28.87,P <0. 05;x2 =4.80,P <0.05)]. Concinsions Compared with CT alone, RT a-chieves better tumor response, local control and survival of patients not only with tumor response but also with local progression after CT. Definitive RT should be the reasonable choice of treatment for early stage extran-odal nasal type NK/T-cell lymphoma.

Analysis of long-term survival related elements in acute promyelocytic leukemia / 白血病·淋巴瘤

Objective To investigate various factors influencing long-term survival of the patients with APL. Methods The clinical data of 62 cases with APL were analyzed retrospectively. Univariate and multivariate analysis of the potential factors influencing survival and prognosis were carried out with Log-Rank and Cox regression method, including sex, age, initial WBC count, initial Plt count, the level of LDH,first induction regimen, length from induction therapy to CR, and post-remission therapy. Results 62 cases were followed up for 6 to 102 months. 5-year OS and relapse-free survival (RFS) were (77.1±6.2)% and (71.4± 3.68)%, respectively.Univariate analysis revealed that initial WBC count, first induction regimen, length from induction therapy to CR and post-remission therapy were important prognostic factors for long-term survival. Multivariate analysis demonstrated that initial WBC count and post-remission therapy were associated with RFS and OS. Conclusion The post-remission therapy combining ATRA, As2O3 and chemotherapy would significantly improve the long-term survival of APL patients entering CR.

Primary nasopharyngeal non-Hodgkin lymphoma and its relationship with Epstein-Barr virus infection / 中华医学杂志(英文版)

<p><b>OBJECTIVES</b>To investigate the immunophenotypes of primary nasopharyngeal non-Hodgkin lymphoma (NPL) and their relationship to Epstein-Barr virus (EBV) infection.</p><p><b>METHODS</b>The clinical data and biopsies of 73 patients with NPL were collected in Guangzhou. In situ hybridization was performed to detect the EBV-encoded small non-polyadenylated nuclear RNAs (EBERs) on biopsy slides. Immunohistochemistry was used to classify the immunophenotypes of NPL and detect EBV antigen expression.</p><p><b>RESULTS</b>Forty-four (60.27%) of the 73 NPLs were of B cell lineage (CD79alpha(+)/CD3(-)/CD56(-)) while the 29 others (39.73%) were of non-B cell lineage. Seventy-three NPLs could be classified into 3 major immunophenotypes: B cell (CD79alpha(+)/CD3(-)/CD56(-), 44 cases), peripheral T cell (CD79alpha(-)/CD3(+)/CD56(-), 22) and NK/T cell (CD79alpha(-)/CD3(+)/CD56(+), 7). The percentages of EBV infection differed among the 3 major immunophenotypes (B cell: 11.36%, 5/44; peripheral T cell: 81.82%, 18/22; NK/T cell: 100%, 7/7). Both CD56(-) positive and CD56(-) negative immunophenotypes could further be divided into 4 subtypes: CD8(-)/CD4(-), CD8(+)/CD4(-), CD8(-)/CD4(+) and CD8(+)/CD4(+). All the CD8(-)/CD4(-) NPLs with CD56(-) positivity (7) or CD56(-) negativity (2) were infected with EBV. The neoplastic cells of a nasopharyngeal Burkitt's lymphoma expressed EBV nuclear antigen 1 (EBNA1) and EBV RNA (EBERs) only. In the other 29 EBV-infected NPLs, most of the lymphoma cells harboring EBV also expressed EBNA1 and EBERs; 21 of the 29 NPLs had a considerable number of neoplastic cells expressing latent membrane protein 1 (LMP1) (21/29, 72.41%) and 23 of 29 NPLs expressed latent membrane protein 2A (LMP2A) (23/29, 79.31%). A few lymphoma cells in 17 (17/29, 58.62%), 23 (23/29, 79.31%) and 22 NPLs (22/29, 75.86%) expressed Zta (Bam HI Z transactivator), viral capsid antigen (VCA) and membrane antigen (MA), respectively.</p><p><b>CONCLUSIONS</b>The prevalence ratio of the 3 immunophenotypes, namely, B cell, peripheral T cell and NK/T cell lymphoma, is about 6:3:1. However, the EBV infection ratio is reversed, 1:8:10. All the NK/T cell (CD56(+)) and peripheral immature T cell (CD3(+)/CD8(-)/CD4(-)) NPLs were EBV-infected. Except for one Burkitt's lymphoma, the EBV harbored in both B cell and non-B cell NPLs was mainly latent infection, type II, expressing EBNA1, LMP1 and LMP2A. However, the EBV found in a few lymphoma cells could become replicative, expressing lytic proteins.</p>

Detection of Epstein-Barr virus DNA in plasma/serum: a useful serological indicator for diagnosis of nasopharyngeal carcinoma / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To compare the detection rates of Epstein-Barr virus (EBV) DNA in the serum/plasma between apparently healthy adults (AHAs) and nasopharyngeal carcinoma (NPC) patients in attempt to evaluate the efficiency of EBV DNA assay for serodiagnosis of NPC.</p><p><b>METHODS</b>The plasma and serum were obtained from 58 AHAs and 66 untreated NPC patients. EBV DNA W-fragment was detected using nested ploymerase chain reaction (PCR). Immunoenzymatic assay for titration of IgA-VCA was also adopted.</p><p><b>RESULTS</b>EBV DNA detection rate (84.85%) in the plasma/serum of 66 NPC patients was significantly higher than that (10.34%) in 58 AHAs. The sensitivity of plasma/serum EBV DNA assay (0.8485) was higher than that (0.8030) of titrating IgA-VCA (positive criterion >/= 1:40) though the specificities of these two tests were the same (0.8966). The correct rate, predictive value of a positive test, and Odds ratio of dual positivity (0.8387, 0.9792 and 141.0, respectively) were higher than those of single positivity either to plasma/serum EBV assay (0.5242, 0.7333 and 1.1423, respectively) or to IgA-VCA >/= 1:40 test (0.4839, 0.5385 and 1.0480, respectively).</p><p><b>CONCLUSION</b>The EBV DNA detection in the plasma/serum using nested PCR may be a useful indicator for serodiagnosis of NPC.</p>