Leukemia Research and Treatment最新文献_第2页

In Vitro Characterization of Valproic Acid, ATRA, and Cytarabine Used for Disease-Stabilization in Human Acute Myeloid Leukemia: Antiproliferative Effects of Drugs on Endothelial and Osteoblastic Cells and Altered Release of Angioregulatory Mediators by Endothelial Cells. 丙戊酸、ATRA和阿糖胞苷用于人类急性髓性白血病疾病稳定的体外表征:药物对内皮细胞和成骨细胞的抗增殖作用以及内皮细胞血管调节介质释放的改变。

Leukemia Research and Treatment Pub Date : 2014-01-01 Epub Date: 2014-01-08 DOI: 10.1155/2014/143479

Hilde Kvestad, Lasse Evensen, James B Lorens, Oystein Bruserud, Kimberley J Hatfield

{"title":"In Vitro Characterization of Valproic Acid, ATRA, and Cytarabine Used for Disease-Stabilization in Human Acute Myeloid Leukemia: Antiproliferative Effects of Drugs on Endothelial and Osteoblastic Cells and Altered Release of Angioregulatory Mediators by Endothelial Cells.","authors":"Hilde Kvestad, Lasse Evensen, James B Lorens, Oystein Bruserud, Kimberley J Hatfield","doi":"10.1155/2014/143479","DOIUrl":"https://doi.org/10.1155/2014/143479","url":null,"abstract":"The combined use of the histone deacetylase inhibitor valproic acid (VPA), the retinoic acid receptor- α agonist all-trans retinoic acid (ATRA), and the deoxyribonucleic acid polymerase- α inhibitor cytarabine (Ara-C) is now considered for disease-stabilizing treatment of acute myeloid leukemia (AML). Leukemogenesis and leukemia cell chemoresistance seem to be supported by neighbouring stromal cells in the bone marrow, and we have therefore investigated the effects of these drugs on primary human endothelial cells and the osteoblastic Cal72 cell line. The results show that VPA and Ara-C have antiproliferative effects, and the antiproliferative/cytotoxic effect of Ara-C was seen at low concentrations corresponding to serum levels found during low-dose in vivo treatment. Furthermore, in functional assays of endothelial migration and tube formation VPA elicited an antiangiogenic effect, whereas ATRA elicited a proangiogenic effect. Finally, VPA and ATRA altered the endothelial cell release of angiogenic mediators; ATRA increased levels of CXCL8, PDGF-AA, and VEGF-D, while VPA decreased VEGF-D and PDGF-AA/BB levels and both drugs reduced MMP-2 levels. Several of these mediators can enhance AML cell proliferation and/or are involved in AML-induced bone marrow angiogenesis, and direct pharmacological effects on stromal cells may thus indirectly contribute to the overall antileukemic activity of this triple drug combination. ","PeriodicalId":18102,"journal":{"name":"Leukemia Research and Treatment","volume":"2014 ","pages":"143479"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/143479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32115775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Molecularly targeted therapies in multiple myeloma. 多发性骨髓瘤的分子靶向治疗

Leukemia Research and Treatment Pub Date : 2014-01-01 Epub Date: 2014-04-16 DOI: 10.1155/2014/976567

Pilar de la Puente, Barbara Muz, Feda Azab, Micah Luderer, Abdel Kareem Azab

{"title":"Molecularly targeted therapies in multiple myeloma.","authors":"Pilar de la Puente, Barbara Muz, Feda Azab, Micah Luderer, Abdel Kareem Azab","doi":"10.1155/2014/976567","DOIUrl":"https://doi.org/10.1155/2014/976567","url":null,"abstract":"Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients will eventually relapse or become refractory to the treatments. Although the treatments have improved, the major problem in MM is the resistance to therapy. Novel agents are currently in development for the treatment of relapsed/refractory MM, including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, cell signaling targeted therapies, and strategies targeting the tumor microenvironment. We have previously reviewed in detail the contemporary immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies therapies for MM. Therefore, in this review, we focused on the role of molecular targeted therapies in the treatment of relapsed/refractory multiple myeloma, including cell signaling targeted therapies (HDAC, PI3K/AKT/mTOR, p38 MAPK, Hsp90, Wnt, Notch, Hedgehog, and cell cycle) and strategies targeting the tumor microenvironment (hypoxia, angiogenesis, integrins, CD44, CXCR4, and selectins). Although these novel agents have improved the therapeutic outcomes for MM patients, further development of new therapeutic agents is warranted. ","PeriodicalId":18102,"journal":{"name":"Leukemia Research and Treatment","volume":"2014 ","pages":"976567"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/976567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32341971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 58

Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies. 儿童淋巴细胞恶性肿瘤中MTHFR多态性与较高的复发/死亡率和延迟的每周MTX给药相关

Leukemia Research and Treatment Pub Date : 2013-01-01 Epub Date: 2013-12-10 DOI: 10.1155/2013/238528

Hiroko Fukushima, Takashi Fukushima, Aiko Sakai, Ryoko Suzuki, Ryoko Nakajima-Yamaguchi, Chie Kobayashi, Atsushi Iwabuchi, Makoto Saito, Ai Yoshimi, Tomohei Nakao, Keisuke Kato, Masahiro Tsuchida, Hideto Takahashi, Kazutoshi Koike, Nobutaka Kiyokawa, Emiko Noguchi, Ryo Sumazaki

{"title":"Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies.","authors":"Hiroko Fukushima, Takashi Fukushima, Aiko Sakai, Ryoko Suzuki, Ryoko Nakajima-Yamaguchi, Chie Kobayashi, Atsushi Iwabuchi, Makoto Saito, Ai Yoshimi, Tomohei Nakao, Keisuke Kato, Masahiro Tsuchida, Hideto Takahashi, Kazutoshi Koike, Nobutaka Kiyokawa, Emiko Noguchi, Ryo Sumazaki","doi":"10.1155/2013/238528","DOIUrl":"https://doi.org/10.1155/2013/238528","url":null,"abstract":"Backgrounds. Outcome of childhood malignancy has been improved mostly due to the advances in diagnostic techniques and treatment strategies. While methotrexate (MTX) related polymorphisms have been under investigation in childhood malignancies, many controversial results have been offered. Objectives. To evaluate associations of polymorphisms related MTX metabolisms and clinical course in childhood lymphoid malignancies. Method. Eighty-two acute lymphoblastic leukemia and 21 non-Hodgkin's lymphoma children were enrolled in this study. Four single nucleotide polymorphisms in 2 genes (MTHFR (rs1801133/c.677C>T/p.Ala222Val and rs1801131/c.1298A>C/p.Glu429Ala) and SLCO1B1 (rs4149056/c.521T>C/p.V174A and rs11045879/c.1865+4846T>C)) were genotyped by Taqman PCR method or direct sequencing. Clinical courses were reviewed retrospectively. Results. No patient who had the AC/CC genotype of rs1801131 (MTHFR) had relapsed or died, in which distribution was statistically different among the AA genotype of rs1801131 (P = 0.004). Polymorphisms of SLCO1B1 (rs11045879 and rs4149056) were not correlated with MTX concentrations, adverse events, or disease outcome. Conclusions. Polymorphisms of MTHFR (rs1801131) could be the plausive candidate for prognostic predictor in childhood lymphoid malignancies. ","PeriodicalId":18102,"journal":{"name":"Leukemia Research and Treatment","volume":"2013 ","pages":"238528"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/238528","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31997669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

New Quantitative Method to Identify NPM1 Mutations in Acute Myeloid Leukaemia. 鉴定急性髓性白血病NPM1突变的新定量方法

Leukemia Research and Treatment Pub Date : 2013-01-01 Epub Date: 2013-04-09 DOI: 10.1155/2013/756703

Sarah Huet, Laurent Jallades, Carole Charlot, Kaddour Chabane, Franck E Nicolini, Mauricette Michallet, Jean-Pierre Magaud, Sandrine Hayette

{"title":"New Quantitative Method to Identify NPM1 Mutations in Acute Myeloid Leukaemia.","authors":"Sarah Huet, Laurent Jallades, Carole Charlot, Kaddour Chabane, Franck E Nicolini, Mauricette Michallet, Jean-Pierre Magaud, Sandrine Hayette","doi":"10.1155/2013/756703","DOIUrl":"https://doi.org/10.1155/2013/756703","url":null,"abstract":"Somatic mutations in the NPM1 gene, which encodes for nucleophosmin, have been reported to be the most frequent genetic abnormalities found in acute myeloid leukaemia (AML). Their identification and quantification remain crucial for the patients' residual disease monitoring. We investigated a new method that could represent a novel reliable alternative to sequencing for its identification. This method was based on high-resolution melting analysis in order to detect mutated patients and on an allele-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) for the identification and quantification of the transcripts carrying NPM1 mutations (NPM1m). Few patients carrying known NPM1m enabled us to set up a table with the different primers' ΔCT values, identifying a profile for each mutation type. We then analysed a series of 337 AML patients' samples for NPM1 mutational status characterization and confirmed the ASO-RQ-PCR results by direct sequencing. We identified some mutations in 86 samples, and the results were fully correlated in 100% of the 36 sequenced samples. We also detected other rare NPM1m in two samples, that we confirmed by direct sequencing. This highly specific method provides a novel quick, useful, and costless tool, easy to use in routine practice.","PeriodicalId":18102,"journal":{"name":"Leukemia Research and Treatment","volume":"2013 ","pages":"756703"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/756703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31445162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

The Impact of FLT3 Mutations on the Development of Acute Myeloid Leukemias. FLT3突变对急性髓性白血病发展的影响。

Leukemia Research and Treatment Pub Date : 2013-01-01 Epub Date: 2013-07-09 DOI: 10.1155/2013/275760

Ugo Testa, Elvira Pelosi

引用次数: 21

Rapid infusion rituximab for maintenance therapy: is it feasible? 快速输注利妥昔单抗维持治疗是否可行?

Leukemia Research and Treatment Pub Date : 2013-01-01 Epub Date: 2013-10-31 DOI: 10.1155/2013/629283

Jolly Patel, Melissa Ho, Viet Ho, Celeste Bello, Benjamin Djulbegovic, Lubomir Sokol, Gene Wetzstein

{"title":"Rapid infusion rituximab for maintenance therapy: is it feasible?","authors":"Jolly Patel, Melissa Ho, Viet Ho, Celeste Bello, Benjamin Djulbegovic, Lubomir Sokol, Gene Wetzstein","doi":"10.1155/2013/629283","DOIUrl":"https://doi.org/10.1155/2013/629283","url":null,"abstract":"Rituximab is an anti-CD-20 monoclonal antibody used in the management of lymphoproliferative disorders. The use of maintenance rituximab has improved progression free survival and overall survival in follicular lymphomas. Although rapid rituximab infusions have been studied extensively, there is little data on the use of rapid infusions during maintenance therapy for low grade lymphomas. The primary objective of this retrospective analysis was to evaluate the incidence of Grade 3 and 4 toxicities with maintenance rapid infusion rituximab according to the Common Terminology Criteria for Adverse Events version 4 (CTC v. 4). Secondary objectives included evaluating all grade infusion related adverse events and correlation of adverse events with varying schedules of rituximab maintenance therapy. All patients who received rapid infusion rituximab as maintenance therapy for low grade lymphoma between December 2007 and November 2011 were included. Rapid rituximab infusions were administered over 90 minutes. Demographic, laboratory and clinical data were collected. A total of 109 patients received 647 rapid rituximab infusions. Three patients experienced an adverse reaction which resulted in one grade 1 infusion reaction and three grade 3 infusion reactions. No patients required hospitalization. All 3 patients received pharmacological and/or supportive care to relieve symptoms associated with the reaction. ","PeriodicalId":18102,"journal":{"name":"Leukemia Research and Treatment","volume":"2013 ","pages":"629283"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/629283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31912522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Physical Activity in Adolescents following Treatment for Cancer: Influencing Factors. 青少年癌症治疗后的身体活动:影响因素

Leukemia Research and Treatment Pub Date : 2013-01-01 Epub Date: 2013-09-18 DOI: 10.1155/2013/592395

Marilyn Wright, Angie Bryans, Kaylin Gray, Leah Skinner, Amanda Verhoeve

{"title":"Physical Activity in Adolescents following Treatment for Cancer: Influencing Factors.","authors":"Marilyn Wright, Angie Bryans, Kaylin Gray, Leah Skinner, Amanda Verhoeve","doi":"10.1155/2013/592395","DOIUrl":"https://doi.org/10.1155/2013/592395","url":null,"abstract":"The purpose of this study was to examine physical activity levels and influencing individual and environmental factors in a group of adolescent survivors of cancer and a comparison group. Methods. The study was conducted using a \"mixed methods\" design. Quantitative data was collected from 48 adolescent survivors of cancer and 48 comparison adolescents using the Godin Leisure-Time Exercise Questionnaire, the Fatigue Scale-Adolescents, and the Amherst Health and Activity Study-Student Survey. Qualitative data was collected in individual semistructured interviews. Results. Reported leisure-time physical activity total scores were not significantly different between groups. Physical activity levels were positively correlated with adult social support factors in the group of adolescent survivors of cancer, but not in the comparison group. Time was the primary barrier to physical activity in both groups. Fatigue scores were higher for the comparison but were not associated with physical activity levels in either group. The qualitative data further supported these findings. Conclusions. Barriers to physical activity were common between adolescent survivors of cancer and a comparative group. Increased knowledge of the motivators and barriers to physical activity may help health care providers and families provide more effective health promotion strategies to adolescent survivors of pediatric cancer. ","PeriodicalId":18102,"journal":{"name":"Leukemia Research and Treatment","volume":" ","pages":"592395"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/592395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40270408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 29

Phase II Study of Bortezomib as a Single Agent in Patients with Previously Untreated or Relapsed/Refractory Acute Myeloid Leukemia Ineligible for Intensive Therapy. 硼替佐米单药治疗先前未治疗或复发/难治性急性髓性白血病不适合强化治疗的II期研究

Leukemia Research and Treatment Pub Date : 2013-01-01 Epub Date: 2013-04-28 DOI: 10.1155/2013/705714

Chiara Sarlo, Francesco Buccisano, Luca Maurillo, Mariagiovanna Cefalo, Luigi Di Caprio, Laura Cicconi, Concetta Ditto, Licia Ottaviani, Ambra Di Veroli, Maria Ilaria Del Principe, Maria Assunta Grasso, Daniela Nasso, Giovanna De Santis, Sergio Amadori, Adriano Venditti

{"title":"Phase II Study of Bortezomib as a Single Agent in Patients with Previously Untreated or Relapsed/Refractory Acute Myeloid Leukemia Ineligible for Intensive Therapy.","authors":"Chiara Sarlo, Francesco Buccisano, Luca Maurillo, Mariagiovanna Cefalo, Luigi Di Caprio, Laura Cicconi, Concetta Ditto, Licia Ottaviani, Ambra Di Veroli, Maria Ilaria Del Principe, Maria Assunta Grasso, Daniela Nasso, Giovanna De Santis, Sergio Amadori, Adriano Venditti","doi":"10.1155/2013/705714","DOIUrl":"https://doi.org/10.1155/2013/705714","url":null,"abstract":"We explored the safety and efficacy of bortezomib given as single agent in patients with untreated or relapsed/refractory acute myeloid leukemia (AML), unfit for conventional chemotherapy. Fourteen patients were treated with bortezomib 1.5 mg/m(2) administered twice weekly for two weeks, every 3 weeks. Median age was 70 years (range 60-81) and the median number of cycles delivered was 2 (range 1-4). Of 13 evaluable patients, in 8 (61%), the administration of bortezomib resulted in an antileukemic effect as demonstrated by peripheral blood and/or bone marrow blast reduction. In 4 (50%) of these 8, a decrease by 37% of transfusion requirement was also observed (P = 0.009). Overall median survival was 4 months (range 0.25-10). Neurotoxicity was the most frequent adverse event with 7 of 13 (54%) patients experiencing grades 3-4 peripheral neuropathy. Neurotoxicity led to treatment discontinuation in 4 (57%) of 7. In conclusion, the observed anti-leukemic activity of bortezomib indicates that there is room for designing additional studies in which combination with other chemotherapeutic agents should be considered. Clinical registration no.: EUDRACT 2006-006923-38.","PeriodicalId":18102,"journal":{"name":"Leukemia Research and Treatment","volume":"2013 ","pages":"705714"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/705714","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31483820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Diffuse large B-cell lymphoma in human T-lymphotropic virus type 1 carriers. 人嗜t淋巴病毒1型携带者的弥漫性大b细胞淋巴瘤

Leukemia Research and Treatment Pub Date : 2012-01-01 Epub Date: 2011-11-09 DOI: 10.1155/2012/262363

Brady E Beltran, Pilar Quiñones, Domingo Morales, Jose C Revilla, Jose C Alva, Jorge J Castillo

引用次数: 11

Is There a Role for HTLV-1-Specific CTL in Adult T-Cell Leukemia/Lymphoma? htlv -1特异性CTL是否在成人t细胞白血病/淋巴瘤中起作用?

Leukemia Research and Treatment Pub Date : 2012-01-01 Epub Date: 2011-11-30 DOI: 10.1155/2012/391953

Aileen G Rowan, Charles R M Bangham

{"title":"Is There a Role for HTLV-1-Specific CTL in Adult T-Cell Leukemia/Lymphoma?","authors":"Aileen G Rowan, Charles R M Bangham","doi":"10.1155/2012/391953","DOIUrl":"https://doi.org/10.1155/2012/391953","url":null,"abstract":"ATLL is an aggressive malignancy of T cells that affects about 5% of individuals infected with HTLV-1. The precise mechanism of oncogenesis is not known, but there is evidence that two regulatory viral proteins, Tax and HBZ, are involved. A high set point proviral load is associated with development of ATLL or a chronic inflammatory condition, HAM/TSP. Several lines of evidence, including HLA class 1 association studies and in vitro killing assays, indicate that cytotoxic T lymphocytes are instrumental in determining this proviral load set point. Prior studies have focused chiefly on the CTL response to the immunodominant Tax protein: efficient lysis of Tax-expressing cells inversely correlates with proviral load in nonmalignant infection. However, a recent study showed that strong binding of peptides from HBZ, but not Tax, to HLA class 1 molecules was associated with a low proviral load and a reduced risk of developing HAM/TSP, indicating an important role for HBZ-specific CTL in determining infection outcome. In comparison with nonmalignant infection, HTLV-1-specific CTLs in ATLL patients are reduced in frequency and functionally deficient. Here we discuss the nature of protective CTL responses in nonmalignant HTLV-1 infection and explore the potential of CTLs to protect against ATLL.","PeriodicalId":18102,"journal":{"name":"Leukemia Research and Treatment","volume":"2012 ","pages":"391953"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/391953","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31138871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17