miR-195/miR-497 Regulate CD274 Expression of Immune Regulatory Ligands in Triple-Negative Breast Cancer / 한국유방암학회지

PURPOSE: Immune suppression is common in patients with advanced breast cancer but the mechanisms underlying this phenomenon have not been sufficiently studied. In this study, we aimed to identify B7 family members that were able to predict the immune status of patients, and which may serve as potential targets for the treatment of breast cancer. We also aimed to identify microRNAs that may regulate the expression of B7 family members. METHODS: The Cancer Genome Atlas data from 1,092 patients with breast cancer, including gene expression, microRNA expression and survival data, were used for statistical and survival analyses. Polymerase chain reaction and Western blot were used to measure messenger RNA and protein expression, respectively. Luciferase assay was used to investigate direct microRNA target. RESULTS: Bioinformatic analysis predicted that microRNA (miR)-93, miR-195, miR-497, and miR-340 are potential regulators of the immune evasion of breast cancer cells, and that they exert this function by targeting CD274, PDCD1LG2, and NCR3LG1. We chose CD274 for further investigations. We found that miR-195, miR-497, and CD274 expression levels were inversely correlated in MDA-MB-231 cells, and miR-195 and miR-497 expressions mimic inhibited CD274 expression in vitro. Mechanistic investigations demonstrated that miR-195 and miR-497 directly target CD274 3′ untranslated region. CONCLUSION: Our data indicated that the level of B7 family members can predict the prognosis of breast cancer patients, and miR-195/miR-497 regulate CD274 expression in triple negative breast cancer. This regulation may further influence tumor progression and the immune tolerance mechanism in breast cancer and may be able to predict the effect of immunotherapy on patients.

Anti-tumor activities and apoptotic mechanism of ribosome-inactivating proteins / 癌症

Ribosome-inactivating proteins (RIPs) belong to a family of enzymes that attack eukaryotic ribosomes and potently inhibit cellular protein synthesis. RIPs possess several biomedical properties, including anti-viral and anti-tumor activities. Multiple RIPs are known to inhibit tumor cell proliferation through inducing apoptosis in a variety of cancers, such as breast cancer, leukemia/lymphoma, and hepatoma. This review focuses on the anti-tumor activities of RIPs and their apoptotic effects through three closely related pathways: mitochondrial, death receptor, and endoplasmic reticulum pathways.

Advances in lymphoma maintenance therapy with rituximab / 中国肿瘤临床

Rituximab is the first monoclonal antibody that has been approved for the treatment of lymphoma. Rituximab has shown significant efficacy in the treatment of B-cell non-Hodgkin's lymphomas, such as diffuse large B-cell and follicular lymphomas. Maintenance therapy with rituximab has further improved the prognosis in patients with follicular lymphoma. These patients responded to induction treatment. This antibody treatment has been recommended in treatment guidelines. The treatment strategy for lymphoma has continuously improved. Recent studies focused on how to improve the definition of the indication for maintenance therapy and how to optimize the current maintenance regimens. In this review, we summarized the main studies and the most recent advances on ritux-imab maintenance therapy in patients with lymphoma.

Research progress of T cell lymphoma: reports from 2014 international conference on T cell lymphoma in clinical treatment / 白血病·淋巴瘤

The treatment status and progress in T cell lymphoma including epigenetic involved mutations that control DNA and histone methylation were reported and intensively discussed in 2014 international T cell lymphoma forum.According to the theory,treatment with HDAC inhibitor belinostat and romidepsin for peripheral T cell lymphoma (PTCL) can achieve 29 ％-38 ％ overall response rate (ORR) and 13.6 months median relief time.NK/T cell lymphoma in southeast asia is a common malignant lymphoma,15 ％-28 ％ of the NHL accounted in China and Japan for,which is significantly higher than that in the European and American countries,mainly related to EB virus widespread infection.L-asparaginase enzymes,such as SMILE and AspMetDex,can make the early cases with more than 70 ％ long-term survival rate,advanced cases with 40 ％ response rate.Some new drugs,such as pralatrexate,combined with romidepsin can be used in PTCL cases to improve the complete remission rate.

A phase II multicenter study to investigate R-ICE as a salvage therapy for relapsed diffuse large B-cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of rituximab together with etoposide, carboplatin, and ifosfamide (R-ICE) as a salvage therapy for relapsed diffuse large B-cell lymphoma (DLBCL) after treatment with rituximab based first-line chemotherapy (R-Chemo).</p><p><b>METHODS</b>DLBCL patients with complete remission (CR) or complete remission unconfirmed (CRu) after 6-8 cycles of R-Chemo treatment but relapsed for first time after stopping treatment were included in this study. Three cycles of R-ICE regimen were given to the patients [1st day: rituximab, 375 mg/m²; 2nd-4th day: ifosfamide, 1 600 mg/m²; 3rd day: carboplatin, area under the curve (AUC) =5 (maximum dosage: 800 mg), 2nd-4th day: etoposide, 100 mg/m²]. The primary endpoint was overall response rate (ORR). The secondary endpoints were the 2-year progression-free survival (PFS), 2-year overall survival (OS), and toxicity.</p><p><b>RESULTS</b>Thirty-two patients with median age at 55(range: 26-68) were recruited in this clinical study and the final analysis. After three cycles of R-ICE salvage treatment, 16 patients (50.0%) achieved CR or CRu and 9 patients (28.1 %) achieved partial remission (PR). The ORR was 78.1%. The 2-year PFS and OS were 40.8% and 60.7%, respectively. Nineteen patients (59.4%) had 3/4 grade adverse events. The ratios of leukopenia neutropenia, anemia and thrombocytopenia in patients with 3/4 grades were 37.5%, 15.6%, and 37.5%, respectively. No patient died.</p><p><b>CONCLUSION</b>R-ICE is an effective salvage therapy for R-Chemo relapsed DLBCL with manageable toxicities.</p>

Long-term Outcomes of Patients with Newly Diagnosed NK/T-cell Lymphoma Treated by EPOCH Regimen / 中山大学学报(医学科学版)

[Objective]This study was aimed to evaluate treatment outcomes and toxicity of continuous-infusion EPOCH regimen for NK/T-cell lymphoma(NK/TCL).[Methods]From June 2003 to June 2008,34 patients including 30 nasal NK/TCL (88.2%)and 4 nasal type NK/TCL(11.8%)received doxorubicin,vincfistine,etoposide over 96 hours infusion with bolus eyelophosphamide and oral predinisone(EPOCH)chemotherapy as first-line treatment.Median cycles of EPOCH administered were 2.5(1-6 cycles).Additional involved field radiation therapy(IFRT)was administered to patients with localized nasal focus after chemotherapy.[Results]Among 34 patients,33 were eligible for response evaluation.The response rate(RR)was 60.6% (20/33)with complete remission(CR)rate of 45.5%(15/33).The RR of patients with nasal NK/TCL was 66.7%(20/30)with CR rate of 50%(15/30).Only one of the 3 nasal type NK/TCL patients achieved stable disease(SD),the other 2 had progressive disease(PD)during chemotherapy.After a median follow-up of 22(2-68)months,the estimated 3-year overall survival rate(OS)was 52.2%.For patients with nasal NK/TCL,the estimated median survival time was not reached,the 3-year OS was 59.4%.For patients with nasal type NK/TCL,the estimated median survival time was only 7 months.The CR rate was 75.0% for localized nasal NK/TCL who received initial EPOCH chemotherapy followed IFRT with the 3-year OS of 75.0%.Major adverse effect was myelosuppression.The incidence of grade Ⅲ～Ⅳ neutropenia was 30.9%.No treatment-related mortality occurred.[Conclusions]EPOCH regiment was effective and well tolerant for nasal NK/TCL.Combined EPOCH chemotherapy followed by IFRT produced promising outcome for patients with localized disease.However,patients with nasal type NK/TCL responded poorly and more efficacious treatment strategies are urgently needed.

Analysis of clinicopathological characteristics and prognosis for triple negative breast cancer / 中国癌症杂志

Background and purpose: Triple negative breast cancer (TNBC) is a high risk breast cancer characterized by the negative expression of estrogen receptor(ER), progesterone receptor (PR) and Her-2 that have no specific therapy. This study was to analyze clinical pathological characteristics, survival, and prognostic factors of patients with TNBC. Methods: Clinical and pathological as well as follow-up data of TNBC, treated at the Cancer Centre of Sun Yat-sen University from Jan. 2000 to Dec. 2003, were collected and analyzed. Results: A total number of 128 women were identified as having triple negative breast cancer. The median age of these patients was 46 years, and 60.9% of them had stage Ⅰ or Ⅱ disease. The majority of pathological types were invasive ductal carcinomas, and 78.1% of tumors were staged T1 or T2. And 48.4% of these patients were involved in lymph node. Event-free survival, local replase-free survival, distant metastasis-free survival and overall survival at five years were 71.1%, 84.3%, 75.8% and 83.6% respectively. Though lymph node metastasis, tumor masses, stage and lymph-vascular invasion were all found to be related to overall survival, however, only lymph node metastasis and tumor masses affected the overall survival as revealed by the Cox proportional hazard model analysis. Conclusion: Triple negative breast cancer has distinct clinical and pathological characteristics. The patients are usually young, with large masses, lymph node metastasis, family history of breast cancer and poor prognosis; lymph node metastasis and tumor mass are important prognostic factors.

Efficacy and safety evaluation for 28 Chinese non-Hodgkin lymphoma patients treated with Hyper-CVAD/MA regimen / 肿瘤研究与临床

Objective To evaluate the efficacy and safety of the hyper-CVAD/MA regimen as an intensified treatment option for 28 T cell and aggressive/highly aggressive B cell NHL in Chinese patients. Methods Clinical data of 28 NHL patients treated with hyper-CVAD/MA regimen from Jan 2005 to Sep 2008 were retrospectively analyzed. Results 27 NHL patients were available for the efficacy analysis, with a response rate of 70.4 %. For the 13 B cell lymphoma cases, the response rate was 84.6 %. The main toxicity was Grade Ⅲ or Grade Ⅳ myelosuppression in all cases and 2 treatment related deaths. Conclusion Hyper-CVAD/MA regimen had a high response rate in T cell and aggressive /highly aggressive B cell NHL lymphoma, companied by significant toxicity when treating Chinese patients. Further clinical practices are needed to pick up a suitable dose which can balance efficacy and safety.

Effect of silencing cyclin D1 gene on chemotherapeutic drug sensitivity in K562 cells in vitro / 肿瘤研究与临床

Objective Cyclin D1 gene plays a significant role in regulating cell cycle progression.It is reported that over-expression of cyclin D1 gene is intimately associated with origination,development and prognosis of tumor and is associated with tumor cells resistance to chemotherapy drug.Suppression of cyclin D1 protein expression leads to cellular chemosensitization.This study was to determine whether this effect also existed in chronic leukemia cell line K562 by inhibiting the expression of cyclin D1 protein through RNA interference.Methods Plasmid vectors expressing small hairpin RNA (shRNA) targeting at cyclin D1 gene were constructed and transfected into K562 cells by chitosan.Cyclin D1 protein was examined using Western Blotting analysis.The cell cycle and apoptosis were determined by flow cytometry.Cellular chemosensitization was evaluated by MTY assay.Results Expression of cyclin D1 protein was markedly down-regulated after transfection with pshRNA-419 and pshRNA-575 at 48 h.Down-regulation of cyclin D1 protein could affect the redistribution of cell cycle,induce apoptosis of K562 cells,decrease 50％inhibitoryconcentration (IC50) of adriamycin and enhance cellular chemosensitization.But there had no above biological effects observed after transfection with blank vector and control vector of m-pshRNA-790 at 48 h.ConclusionK562 cells could be chemosensitized by the down-regulation of cyclin D1 expression through RNA interference.

Apoptosis induced by DNA primase inhibitor 3,3'-diethyl-9-methylthia-carbocyanine iodide in human leukemia HL-60 cells / 药学学报

Aim To investigate apoptosis induced by 3,3'-diethyl-9-methylthia-carbocyanine iodide(DMTCCI) , an inhibitor of DNA primase found in our previous study, and the mechanism of DMTCCI in human myelogenous leukemia HL-60 cells. Methods HL-60 cells were cultured in RPMI-1640 medium and treated with different concentrations of DMTCCI. MTT assay was used to detect growth inhibition.Flow cytometry and DNA ladders were used to detect apoptosis. Western blotting was used to observe the expression of survivin, Bcl-xL, Bad, Bax, Bcl-2, caspase-9, caspase-3, caspase-6, PARP, DFF45 and lamin B protein. Caspase-3 activity was measured by ApoAlert Caspase-3 Assay Kit. Results DMTCCI inhibited proliferation of human leukemia HL-60 cells with IC50 value of 0. 24 μmol · L-1. The results of flow cytometry and DNA ladders showed that DMTCCI could induce apoptosis of HL-60 cells. The expression levels of protein survivin and Bcl-xL were down-regulated, Bad and Bax were up-regulated,while Bcl-2 protein had no change in response to DMTCCI treatment in HL-60 cells. Treatment of HL-60cells with DMTCCI induced the proteolytic cleavage of caspase-9, caspase-3, caspase-6, PARP, DFF45and lamin B protein. Caspase-3 activity apparently increased at 3 h and reached a peak at 12 h after exposure to 1 μmol · L-1 of DMTCCI in HL-60 cells. Conclusion DMTCCI inhibited proliferation and induced apoptosis of human leukemia HL-60 cells. Bcl-2 family proteins, survivin and caspases family proteins might playa role in the apoptosis process induced by DMTCCI.