This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ http://www.jhoonline.org The latest articles from Journal of Hematology & Oncology (ISSN 1756-8722) published by BioMed Central At the plenary session of the 2008 annual meeting of the American Society of Clinical Oncology, updated results were presented from a large randomized phase III trial comparing adjuvant radiation therapy (RT) and one cycle of Carboplatin for the adjuvant treatment of Stage I seminoma. Results of this Medical Research Council (MRC) trial led its investigators to conclude that one cycle of carboplatin was equivalent in safety and efficacy and less toxic than RT. In this editorial, the trial's design, statistics, toxicity, and length of follow-up are discussed within the context of historical treatments of this disease. With a 1.3% increase in relapse rate (5.3% with carboplatin vs. 4.0% with radiation), a 3% or greater increase in relapse rate could not be excluded, the primary endpoint of the study. A decrease in second testicular germ cell tumors was observed, but was equivalent to the increase in relapse rate. Acute toxicity was generally less with carboplatin. However, the extent of late toxicity, including late second neoplasms, cannot be evaluated because of the short median follow-up. Carboplatin is not yet a standard of care. Surveillance-based strategies, including risk-adapted policies that limit RT to patients with the greatest likelihood of relapse remain prudent at this time. http://www.jhoonline.org/content/1/1/22 Darren R Feldman and George J Bosl Journal of Hematology & Oncology 2008, 1:22 2008-11-07 doi:10.1186/1756-8722-1-22 Journal of Hematology & Oncology 1756-8722 1 22 2008-11-07 Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation. http://www.jhoonline.org/content/1/1/21 Yiu-Keung Lau, Manpreet K Chadha, Alan Litwin and Donald L Trump Journal of Hematology & Oncology 2008, 1:21 2008-11-05 doi:10.1186/1756-8722-1-21 Journal of Hematology & Oncology 1756-8722 1 21 2008-11-05 This review summarizes phase I trial results of 11 drugs presented at the American Society of Clinical Oncology meeting held in Chicago IL from May 30 to June 3rd 2008: BMS-663513, CT-322, CVX-045, GDC-0449, GRN163L, LY2181308, PF-00562271, RAV12, RTA 402, XL765, and the survivin vaccine. http://www.jhoonline.org/content/1/1/20 Andrea Molckovsky and Lillian L Siu Journal of Hematology & Oncology 2008, 1:20 2008-10-29 doi:10.1186/1756-8722-1-20 Journal of Hematology & Oncology 1756-8722 1 20 2008-10-29 Background: Excessive maturation of hematopoietic cells leads to a reduction of long-term proliferative capability during cord blood (CB) expansion. In this study, we report the effects of anit-CD52 (Alemtuzumab, Campath) on both short- and long-term ex vivo expansion of CB hematopoietic stem cells (HSC) by evaluating the potential role of Alemtuzumab in preserving the repopulating capability in CB HSC and nonlymphoid progenitors. Methods: Ex vivo expansion experiments were carried out using freshly purified CB CD34+ cells in StemSpan™ SFEM medium in the presence of stem cell factor, Flt3-Ligand and thrombopoietin at 50 ng/ml. Alemtuzumab (10 μg/ml) was used to deplete CD52+ cells during the cultures. Flow cytometry was used to monitor CB HSC and their differentiation. Colony forming unit (CFU) assays and long term culture-initiating cell (LTC-IC) assays were performed on cells obtained from day 0 (before culture) and day 14 after cultures. Secondary cultures was performed using CD34+ cells isolated at 35 days from primary cultures and further cultured in StemSpan™ SFEM medium for another 14 days to confirm the long term effect of alemtuzumab in liquid cultures. Results: Compared to cytokines alone, addition of alemtuzumab resulted in a significant increase in total nucleated cells, absolute CD34+ cells, myeloid and megakaryocytic progenitors, multi-lineage and myeloid CFU and LTC-IC. Conclusion: The results from current study suggested that the use of alemtuzumab for ex vivo expansion of CBHSC maybe advantageous. Our findings may improve current technologies for CBHSC expansion and increase the availability of CB units for transplantation. However, in vivo studies using animal models are likely needed in further studies to test the hematopoietic effects using such expanded CB products. http://www.jhoonline.org/content/1/1/19 Che K Lim, Li Sun, Qi Feng, Ping Law, Wei T Chua, Shy N Lim and William YK Hwang Journal of Hematology & Oncology 2008, 1:19 2008-10-23 doi:10.1186/1756-8722-1-19 Journal of Hematology & Oncology 1756-8722 1 19 2008-10-23 Hepatocellular carcinoma is rare, but increasing in prevalence in the United States. Recent studies have shown that sorafenib, a multikinase inhibitor, can reduce tumor progression in patients with this cancer. However, complete remission has not been observed. We report a case of a 78-year old patient with unresectable metastatic hepatocellular carcinoma who had a rapid and complete clinical response following therapy with sorafenib for six months. No evidence of disease recurrence has been noted for 6 months after discontinuation of therapy. http://www.jhoonline.org/content/1/1/18 Brian J So, Tanios Bekaii-Saab, Mark A Bloomston and Tushar Patel Journal of Hematology & Oncology 2008, 1:18 2008-10-17 doi:10.1186/1756-8722-1-18 Journal of Hematology & Oncology 1756-8722 1 18 2008-10-17 Objectives We have analyzed t(12;21)(p13:q22) in an attempt to evaluate the frequency and prognostic significance of TEL-AML1 fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH). Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD). Methods: All bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH) for t(12;21) in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD). We determined the prognostic significance of TEL-AML1 fusion represented by disease course and survival. Results: TEL-AML1 fusion gene was positive in (37.5%) in newly diagnosed patients. There was a significant correlation between TEL-AML1 fusion gene both at diagnosis (r = 0.5, P = 0.003) and as a MRD (r = 0.4, P = 0.01) with favorable course. Kaplan-Meier curve for the presence of TEL-AML1 fusion at the diagnosis was associated with a better probability of overall survival (OS); mean survival time was 47 ± 1 month, in contrast to 28 ± 5 month in its absence (P = 0.006). Also, the persistence at TEL-AML1 fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 ± 2 months in the presence of MRD and it was 40 ± 1 months in its absence. So, persistence of TEL-AML1 fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS. Conclusion: For most patients, the presence of TEL-AML1 fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of TEL-AML1 fusion as MRD has no additive prognostic value. http://www.jhoonline.org/content/1/1/17 Eman Mosad, Hosny B Hamed, Rania M Bakry, Azza M Ezz-Eldin and Nesrine M Khalifa Journal of Hematology & Oncology 2008, 1:17 2008-10-17 doi:10.1186/1756-8722-1-17 Journal of Hematology & Oncology 1756-8722 1 17 2008-10-17 IntroductionBreast cancer is the most common female cancer and the second most common cause of female cancer-related deaths in the United States. World-wide, more than one million women will be diagnosed with breast cancer annually. In 2007, more than 175,000 women were diagnosed with breast cancer in the United States. However, deaths due to breast cancer have decreased in the recent years in part because of improved screening techniques, surgical interventions, understanding of the pathogenesis of the disease, and utilization of traditional chemotherapies in a more efficacious manner. One of the more exciting areas of improvement in the treatment of breast cancer is the entrance of novel therapies now available to oncologists. In the field of cancer therapeutics, the area of targeted and biologic therapies has been progressing at a rapid rate, particularly in the treatment of breast cancer.Since the advent of imatinib for the successful treatment of chronic myelogenous leukemia in the 2001, clinicians have been searching for comparable therapies that could be as efficacious and as tolerable. In order for targeted therapies to be effective, the agent must be able to inhibit critical regulatory pathways which promote tumor cell growth and proliferation. The targets must be identifiable, quantifiable and capable of being interrupted.In the field of breast cancer, two advances in targeted therapy have led to great strides in the understanding and treatment of breast cancer, namely hormonal therapy for estrogen positive receptor breast cancer and antibodies directed towards the inhibition of human epidermal growth factor receptor (HER)2. These advances have revolutionized the understanding and the treatment strategies for breast cancer. Building upon these successes, a host of novel agents are currently being investigated and used in clinical trials that will hopefully prove to be as fruitful. This review will focus on novel therapies in the field of breast cancer with a focus on metastatic breast cancer (MBC) and updates from the recent annual ASCO meeting and contains a summary of the results. http://www.jhoonline.org/content/1/1/16 David Chu and Janice Lu Journal of Hematology & Oncology 2008, 1:16 2008-10-01 doi:10.1186/1756-8722-1-16 Journal of Hematology & Oncology 1756-8722 1 16 2008-10-01 Imatinib was the first BCR-ABL-targeted agent approved for the treatment of patients with chronic myeloid leukemia (CML) and confers significant benefit for most patients; however, a substantial number of patients are either initially refractory or develop resistance. Point mutations within the ABL kinase domain of the BCR-ABL fusion protein are a major underlying cause of resistance. Of the known imatinib-resistant mutations, the most frequently occurring involve the ATP-binding loop (P-loop). In vitro evidence has suggested that these mutations are more oncogenic with respect to other mutations and wild type BCR-ABL. Dasatinib and nilotinib have been approved for second-line treatment of patients with CML who demonstrate resistance (or intolerance) to imatinib. Both agents have marked activity in patients resistant to imatinib; however, they have differential activity against certain mutations, including those of the P-loop. Data from clinical trials suggest that dasatinib may be more effective vs. nilotinib for treating patients harboring P-loop mutations. Other mutations that are differentially sensitive to the second-line tyrosine kinase inhibitors (TKIs) include F317L and F359I/V, which are more sensitive to nilotinib and dasatinib, respectively. P-loop status in patients with CML and the potency of TKIs against P-loop mutations are key determinants for prognosis and response to treatment. This communication reviews the clinical importance of P-loop mutations and the efficacy of the currently available TKIs against them. http://www.jhoonline.org/content/1/1/15 Shundong Cang and Delong Liu Journal of Hematology & Oncology 2008, 1:15 2008-10-01 doi:10.1186/1756-8722-1-15 Journal of Hematology & Oncology 1756-8722 1 15 2008-10-01 Background: L-arginine is the common substrate for the two isoforms of arginase. Arginase I, highly expressed in the liver and arginase II mainly expressed in the kidney. Arginase I-producing myeloid derived suppressor cells have been shown to inhibit T-cell function by the depletion of L-arginine. On the other hand, arginase II has been detected in patients with cancer and is thought to metabolize L-arginine to L-ornithine needed to sustain rapid tumor growth; however its role in L-arginine depletion is unclear. Thus, in tumor biology, L-arginine metabolism may play a dual role in tumor growth and in the induction of T cell dysfunction. Therefore, we studied in murine renal cell carcinoma (RCC) cell lines, the effect of arginase II on tumor cell proliferation and L-arginine depletion. The effect of arginase inhibitors on cell proliferation was also tested. Methods: Three murine renal cell carcinoma (mRCC) cell lines were tested for the presence of arginase. nor-NOHA, an arginase inhibitor was used to substantiate the effect of arginase on cell growth and L-arginine depletion. Amino acid levels were tested by HPLC. Results: Our results show that mRCC cell lines express only arginase II and were able to deplete L-arginine from the medium. Cell growth was independent of the amount of arginase activity expressed by the cells. nor-NOHA significantly (P = 0.01) reduced arginase II activity and suppressed cell growth in cells exhibiting high arginase activity.The depletion of L-arginine by mRCC induced the decrease expression of CD3ζ a key element for T-cell function. Conclusion: The results of this study show for the first time that arginase II produced by RCC cell lines depletes L-arginine resulting in decreased expression of CD3ζ. These results indicate that RCC cell lines expressing arginase II can modulate the L-arginine metabolic pathway to regulate both cell growth and T-cell function. Blocking arginase may lead to a decrease in RCC cell growth and aid in restoring immune function by increasing L-arginine availability for T-cell use. Understanding the interplay between arginase II and its interaction with the immune system may provide future therapeutic benefits to treat patients with RCC. http://www.jhoonline.org/content/1/1/14 David J Tate, Derek J Vonderhaar, Yupanqui A Caldas, Toye Metoyer, John R Patterson, Diego H Aviles and Arnold H Zea Journal of Hematology & Oncology 2008, 1:14 2008-09-25 doi:10.1186/1756-8722-1-14 Journal of Hematology & Oncology 1756-8722 1 14 2008-09-25 The most common semiquantitative method of evaluation of pulmonary lesions using 18F-FDG PET is FDG standardized uptake value (SUV). An SUV cutoff of 2.5 or greater has been used to differentiate between benign and malignant nodules. The goal of our study was to investigate the correlation between the size of pulmonary nodules and the SUV for benign as well as for malignant nodules. Methods: Retrospectively, 173 patients were selected from 420 referrals for evaluation of pulmonary lesions. All patients selected had a positive CT and PET scans and histopathology biopsy. A linear regression equation was fitted to a scatter plot of size and SUVmax for malignant and benign nodules together. A dot diagram was created to calculate the sensitivity, specificity, and accuracy using an SUVmax cutoff of 2.5. Results: The linear regression equations and (R2)s as well as the trendlines for malignant and benign nodules demonstrated that the slope of the regression line is greater for malignant than for benign nodules. Twenty-eight nodules of group one (≤ 1.0 cm) are plotted in a dot diagram using an SUVmax cutoff of 2.5. The sensitivity, specificity, and accuracy were calculated to be 85%, 36% and 54% respectively. Similarly, sensitivity, specificity, and accuracy were calculated for an SUVmax cutoff of 2.5 and found to be 91%, 47%, and 79% respectively for group 2 (1.1–2.0 cm); 94%, 23%, and 76%, respectively for group 3 (2.1–3.0 cm); and 100%, 17%, and 82%,, respectively for group 4 (> 3.0 cm). The previous results of the dot diagram indicating that the sensitivity and the accuracy of the test using an SUVmax cutoff of 2.5 are increased with an increase in the diameter of pulmonary nodules. Conclusion: The slope of the regression line is greater for malignant than for benign nodules. Although, the SUVmax cutoff of 2.5 is a useful tool in the evaluation of large pulmonary nodules (> 1.0 cm), it has no or minimal value in the evaluation of small pulmonary nodules (≤ 1.0 cm). http://www.jhoonline.org/content/1/1/13 Majid Khalaf, Hani Abdel-Nabi, John Baker, Yiping Shao, Dominick Lamonica and Jayakumari Gona Journal of Hematology & Oncology 2008, 1:13 2008-09-22 doi:10.1186/1756-8722-1-13 Journal of Hematology & Oncology 1756-8722 1 13 2008-09-22