Science News, Information and Educational Resources


Science Feed Image

    		•    
    BACKGROUND:Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited.METHODS:The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m2 vs 30 mg/m2 daily × 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts.RESULTS:The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m2 and 29% at 30 mg/m2). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m2 of clofarabine. Myelosuppression and infectious complications were frequent.CONCLUSIONS:Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued. Cancer 2011;. © 2011 American Cancer Society.dx.doi.org


      ...Read On

    BACKGROUND:Despite the high complete response rates achieved with fludarabine-based regimens, relapse is inevitable in chronic lymphocytic leukemia (CLL). Relapsed patients often acquire deletions of the short arm of chromosome 17 (del[17p]), which are closely associated with tumor protein 53 (TP53) mutations. Wild-type p53 up-regulates and activates B-cell CLL/lymphoma 2 (BCL-2)-associated X protein (BAX), and it down-regulates and inactivates BCL-2. The small-molecule BCL-2 inhibitor ABT-737 induces apoptosis in a BAX-dependent and BCL-2 homologous antagonist-killer (BAK)-dependent manner. The role of p53 in sensitivity of CLL cells to BCL-2 inhibition has not been extensively investigated.METHODS:The authors investigated the association of del(17p) with ABT-737 sensitivity in CLL cells from 50 patients. Stable p53 and BAX knockdown cells were used for mechanistic studies.RESULTS:CLL cells with del(17p) were less sensitive to ABT-737-induced BAX activation and apoptosis than CLL cells without del(17p) (39% ± 7.3% vs 63.7% ± 2.9% [specific annexin V induction]; P < .01). A positive correlation between the degrees of apoptosis induced by ABT-737 and by the p53-activating binding protein homolog murine double minute (MDM2) antagonist nutlin-3a (correlation coefficient [r] = 0.75; P < .0001) was observed. CLL cells with del(17p) expressed lower levels of BAX than those without del(17p) (0.67 ± 0.12 vs 1.27 ± 0.10 in relative protein expression levels; P < .01). Knockdown of p53 or BAX in leukemia cells resulted in decreased apoptosis induced by ABT-737.CONCLUSIONS:The current data indicated that p53 dysfunction may lead to decreased apoptosis induction by ABT-737. Cancer 2011;. © 2011 American Cancer Society.dx.doi.org


      ...Read On

    BACKGROUND:The efficacy of azacitidine for the treatment of high-risk myelodysplastic syndromes has prompted the issue of its potential role even in the treatment of acute myeloid leukemia (AML).METHODS:The authors analyzed 82 patients with AML who were diagnosed according to World Health Organization criteria. The median patient age was 72 years (range, 29-87 years), and 27 patients (33%) had secondary AML. Of 62 patients with evaluable cytogenetics, 18 patients (29%) had a poor-risk karyotype, and 44 patients (71%) had an intermediate karyotype. Thirty-five patients (43%) received azacitidine as front-line treatment, and 47 patients (57%) had previously received 1 or more line of chemotherapy.RESULTS:The overall response rate was 32% (26 of 82 patients) and included 12 (15%) complete remissions (CRs), 4 (5%) CRs with incomplete blood count recovery (CRi), and 10 (12%) partial responses (PRs). Responses were observed more frequently among untreated patients compared with pretreated patients; in fact, 17 of 35 untreated patients (48%) responded, including 11 responses (31%) classified as CR/CRi. Conversely, only 9 of 47 pretreated patients (19%) responded, including 5 responses (11%) that were classified as CR/Cri. The response rate was significantly higher for untreated patients (P = .006) and those who had white blood cell counts <10 × 109/L (P = .006). For untreated patients who achieved a response, the median overall response duration was 13 months, and the 1-year and 2-years overall survival rates were 58% and 24%, respectively.CONCLUSIONS:The current results indicated that azacitidine promises to be an effective therapy for elderly patients with untreated AML and with white blood cell counts <10 × 109/L. Cancer 2011;. © 2011 American Cancer Society.dx.doi.org


      ...Read On

    BACKGROUND:The aim of this study was to determine whether circulating C-reactive protein (CRP) levels before treatment predict the overall survival and disease-free survival in soft tissue sarcoma patients.METHODS:A total of 102 primary soft tissue sarcoma patients from 2003 to 2009 were retrospectively reviewed. The CRP levels were obtained before treatment for all patients. The patients who presented with metastases at diagnosis were excluded from this study.RESULTS:Elevated CRP levels were seen in 18 patients. The tumor histological grade and American Joint Committee on Cancer stage in the patients with elevated CRP levels were significantly higher than those in patients with normal CRP levels. Patients with elevated CRP levels before initial treatment had a poorer overall survival than patients with normal CRP levels (P = .01). The overall survival estimates at 3 and 5 years were 75.3% and 53.8%, respectively, versus 90.3% and 81.3%, respectively. Patients with elevated CRP levels before initial treatment had poorer event-free survival after initial treatment than patients with normal CRP levels (P < .001). The event-free survival estimates at 2 and 5 years were 53.2% and 33.2%, respectively, versus 83.2% and 81.3%, respectively. A multivariate analysis also showed the preoperative CRP level to be an independent predictor of events.CONCLUSIONS:The pretreatment serum CRP level may be a marker of aggressive tumor characteristics. Pretreatment elevated CRP levels were found to be a poor prognostic factor for overall survival in a univariate analysis, and for disease-free survival in a multivariate analysis, for soft tissue sarcoma patients. Cancer 2011;. © 2011 American Cancer Society.dx.doi.org


      ...Read On

    BACKGROUND:DEAD box 1 (DDX1) is an RNA helicase with a number of roles, including translation initiation, RNA splicing and modification, and possibly DNA double-strand break repair. Amplification of DDX1 expression has been implicated in tumors including neuroblastoma, Wilms tumor, retinoblastoma, and testicular carcinoma. The purpose of this study was to evaluate the prognostic significance of DDX1 expression in patients with breast cancer treated with breast-conserving therapy.METHODS:Paraffin-embedded specimens from 282 women with node-negative stage 1 and 2 breast cancer treated with breast-conserving surgery and radiation therapy were constructed into tissue microarrays and stained for DDX1. The molecular profiles were correlated with clinicopathologic factors and overall, local, and distant metastatic-free survival.RESULTS:DDX1 positivity was identified in 142 (50%) patients. The median age at diagnosis was 53 years. Eighty percent of the patients had T1 disease; 11% were HER2neu-positive, and 18% had triple-negative disease. DDX1 negativity was strongly associated with triple-negative phenotype (P = .01). DDX1 positivity was found to be associated with improved local relapse-free survival (96% vs 85%, P = .0233), distant metastatic-free survival (95% vs 85%, P = .0320), and overall survival (92% vs 84%, P = .0474) at 10 years.CONCLUSIONS:Node-negative, early stage breast cancer patients with high levels of DDX1 were found to have a significant improvement in local control, distant metastatic-free survival, and overall survival compared with patients with low levels of DDX1. Cancer 2011;. © 2011 American Cancer Society.dx.doi.org


      ...Read On


    		   
    You can link to this article on your web site using following code:

    Website Code:

    Forum Code:  




     
    		 
    Comments

    We're looking for comments that are interesting, substantial or highly amusing. If your comments are excessively self-promotional (use your real name, no keywords please), obnoxious, or even worse, boring, you will be banned from commenting. Your comment must be related to the post. Please do not comment on how great or wonderful the post is. All comments are moderated and, if approved, will display in less than 24 hours.


    blog comments powered by Disqus