http://www.jhoonline.org The most accessed research articles published by Journal of Hematology & Oncology 2011-12-22T00:00:00Z Mast cell activation disease comprises disorders characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells' mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. In most cases of mast cell activation disease, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitively diagnosed major illness does not well account for the entirety of the patient's presentation. http://www.jhoonline.org/content/4/1/10 Gerhard Molderings Stefan Brettner Jurgen Homann Lawrence Afrin Journal of Hematology & Oncology 2011, null:10 2011-03-22T00:00:00Z doi:10.1186/1756-8722-4-10 /content/figures/1756-8722-4-10-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 10 2011-03-22T00:00:00Z XML Dabigatran is an emerging oral anticoagulant which is a direct inhibitor of thrombin activity. It has been approved in the European Union and the United States of America for the prevention of thrombosis after major orthopedic surgery. It has also been approved by the American Food and Drug Administration and the European Medicines Agency for the prevention of stroke in chronic atrial fibrillation. Dabigatran provides a stable anticoagulation effect without any need to perform periodical laboratory controls. Of note, there is a growing amount of clinical evidence which shows its safety and efficacy. For these reasons, dabigatran may suppose a revolution in oral anticoagulation. However, two important limitations remain. First, it is contraindicated in patients with end-stage renal disease. Second, there is no evidence of the prevention of thrombosis in mechanical heart valves. http://www.jhoonline.org/content/4/1/53 Santiago Redondo Maria-Paz Martinez Marta Ramajo Jorge Navarro-Dorado Abelardo Barez Teresa Tejerina Journal of Hematology & Oncology 2011, null:53 2011-12-21T00:00:00Z doi:10.1186/1756-8722-4-53 /content/figures/1756-8722-4-53-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 53 2011-12-21T00:00:00Z XML Non-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as β-glucans. β-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, β-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages, neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and adaptive response can be modulated by β-glucans and they can also enhance opsonic and non-opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 1→3 linear β-glycosidic chain of β-glucans cannot be digested. Most β-glucans enter the proximal small intestine and some are captured by the macrophages. They are internalized and fragmented within the cells, then transported by the macrophages to the marrow and endothelial reticular system. The small β-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses. However, β-glucans of different sizes and branching patterns may have significantly variable immune potency. Careful selection of appropriate β-glucans is essential if we wish to investigate the effects of β-glucans clinically. So far, no good quality clinical trial data is available on assessing the effectiveness of purified β-glucans among cancer patients. Future effort should direct at performing well-designed clinical trials to verify the actual clinical efficacy of β-glucans or β-glucans containing compounds. http://www.jhoonline.org/content/2/1/25 Godfrey Chi-Fung Chan Wing Keung Chan Daniel Man-Yuen Sze Journal of Hematology & Oncology 2009, null:25 2009-06-10T00:00:00Z doi:10.1186/1756-8722-2-25 /content/figures/1756-8722-2-25-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 25 2009-06-10T00:00:00Z XML Immunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide is a 4-amino-glutamyl analogue of thalidomide that lacks the neurologic side effects of sedation and neuropathy and has emerged as a drug with activity against various hematological and solid malignancies. It is approved by FDA for clinical use in myelodysplastic syndromes with deletion of chromosome 5q and multiple myeloma. Lenalidomide has been shown to be an immunomodulator, affecting both cellular and humoral limbs of the immune system. It has also been shown to have anti-angiogenic properties. Newer studies demonstrate its effects on signal transduction that can partly explain its selective efficacy in subsets of MDS. Even though the exact molecular targets of lenalidomide are not well known, its activity across a spectrum of neoplastic conditions highlights the possibility of multiple target sites of action. http://www.jhoonline.org/content/2/1/36 Venumadhav Kotla Swati Goel Sangeeta Nischal Christoph Heuck Kumar Vivek Bhaskar Das Amit Verma Journal of Hematology & Oncology 2009, null:36 2009-08-12T00:00:00Z doi:10.1186/1756-8722-2-36 /content/figures/1756-8722-2-36-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 36 2009-08-12T00:00:00Z XML Background: Previous studies demonstrated Ganoderma lucidum polysaccharides (GL-PS), a form of bioactive β-glucan can stimulate the maturation of monocyte-derived dendritic cells (DC). The question of how leukemic cells especially in monocytic lineage respond to GL-PS stimuli remains unclear. Results: In this study, we used in vitro culture model with leukemic monocytic cell-lines THP-1 and U937 as monocytic effectors cells for proliferation responses and DCs induction. We treated the THP-1 and U937 cells with purified GL-PS (100 μg/mL) or GL-PS with GM-CSF/IL-4. GL-PS alone induced proliferative response on both THP-1 and U937 cells but only THP-1 transformed into typical DC morphology when stimulated with GL-PS plus GM-CSF/IL-4. The transformed THP-1 DCs had significant increase expression of HLA-DR, CD40, CD80 and CD86 though not as high as the extent of normal monocyte-derived DCs. They had similar antigen-uptake ability as the normal monocyte-derived DCs positive control. However, their potency in inducing allogeneic T cell proliferation was also less than that of normal monocyte-derived DCs. Conclusion: Our findings suggested that GL-PS could induce selected monocytic leukemic cell differentiation into DCs with immuno-stimulatory function. The possible clinical impact of using this commonly used medicinal mushroom in patients with monocytic leukemia (AML-M4 and M5) deserved further investigation. http://www.jhoonline.org/content/1/1/9 Wing Keung Chan Christopher Cheung Helen Law Yu Lung Lau Godfrey Chan Journal of Hematology & Oncology 2008, null:9 2008-07-21T00:00:00Z doi:10.1186/1756-8722-1-9 /content/figures/1756-8722-1-9-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 9 2008-07-21T00:00:00Z XML Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent. http://www.jhoonline.org/content/2/1/38 Subhash Padhye Aamir Ahmad Nikhil Oswal Fazlul Sarkar Journal of Hematology & Oncology 2009, null:38 2009-09-02T00:00:00Z doi:10.1186/1756-8722-2-38 /content/figures/1756-8722-2-38-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 38 2009-09-02T00:00:00Z XML We reviewed preclinical data and clinical development of MDM2 (murine double minute 2), ALK (anaplastic lymphoma kinase) and PARP (poly [ADP-ribose] polymerase) inhibitors. MDM2 binds to p53, and promotes degradation of p53 through ubiquitin-proteasome degradation. JNJ-26854165 and RO5045337 are 2 small-molecule inhibitors of MDM2 in clinical development. ALK is a transmembrane protein and a member of the insulin receptor tyrosine kinases. EML4-ALK fusion gene is identified in approximately 3-13% of non-small cell lung cancer (NSCLC). Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival. PARPs are a family of nuclear enzymes that regulates the repair of DNA single-strand breaks through the base excision repair pathway. Randomized phase II study has shown adding PARP-1 inhibitor BSI-201 to cytotoxic chemotherapy improves clinical outcome in patients with triple-negative breast cancer. Olaparib, another oral small-molecule PARP inhibitor, demonstrated encouraging single-agent activity in patients with advanced breast or ovarian cancer. There are 5 other PARP inhibitors currently under active clinical investigation. http://www.jhoonline.org/content/4/1/16 Yuan Yuan Yu-Min Liao Chung-Tsen Hsueh Hamid Mirshahidi Journal of Hematology & Oncology 2011, null:16 2011-04-20T00:00:00Z doi:10.1186/1756-8722-4-16 /content/figures/1756-8722-4-16-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 16 2011-04-20T00:00:00Z XML Background: Infantile hemangiomas (IH) are the most common benign tumors of infancy. The typical clinical course consists of rapid growth during the first year of life, followed by natural and gradual involution over a multi-year time span through unknown cellular mechanisms. Some tumors respond to medical treatment with corticosteroids or beta-blockers, however, when this therapy fails or is incomplete, surgical extirpation may be necessary. Noninvasive therapies to debulk or eliminate these tumors would be an important advance. The development of an in vitro cell culture system and an animal model would allow new insights into the biological processes involved in the development and pathogenesis of IH. Results: We observed that proliferative stage IH specimens contain significantly more SALL4+ and CD133+ cells than involuting tumors, suggesting a possible stem cell origin. A tumor sphere formation assay was adapted to culture IH cells in vitro. Cells in IH tumor spheres express GLUT1, indicative of an IH cell of origin, elevated levels of VEGF, and various stem/progenitor cell markers such as SALL4, KDR, Oct4, Nanog and CD133. These cells were able to self-renew and differentiate to endothelial lineages, both hallmarks of tumor stem cells. Treatment with Rapamycin, a potent mTOR/VEGF inhibitor, dramatically suppressed IH cell growth in vitro. Subcutaneous injection of cells from IH tumor spheres into immunodeficient NOD-SCID mice produced GLUT1 and CD31 positive tumors with the same cellular proliferation, differentiation and involution patterns as human hemangiomas. Conclusions: The ability to propagate large numbers of IH stem cells in vitro and the generation of an in vivo mouse model provides novel avenues for testing IH therapeutic agents in the future. http://www.jhoonline.org/content/4/1/54 Dan Xu Teresa O Archil Shartava Taylor Fowles Jianchang Yang Louis Fink David Ward Martin Mihm Milton Waner Yupo Ma Journal of Hematology & Oncology 2011, null:54 2011-12-22T00:00:00Z doi:10.1186/1756-8722-4-54 /content/figures/1756-8722-4-54-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 54 2011-12-22T00:00:00Z XML PurposeR-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) have both been used successfully in the treatment of patients with symptomatic follicular lymphoma (FL). No study has compared the efficacy of the two treatment modalities and attempted to evaluate the role of anthracyclines in the management of patients with FL. We conducted a meta-analysis of relevant literature comparing the two treatment arms for FL with response being the final endpoint.Patients and MethodsTwo analyses were conducted: The first analysis compared R-CHOP to R-CVP as frontline agents for the treatment of FL, and the second analysis included both untreated and relapsed patients. Results: For both studies, R-CVP was superior to R-CHOP when evaluating for complete response (CR). Odds ratios were 2.86 (95% CI, 1.81–4.51) in the first analysis and 1.48 (95% CI, 0.991–2.22) in the second analysis. However for overall response (CR+Partial response, PR), R-CHOP was superior, with odds ratios of 5.45 (95% CI: 2.51 – 11.83) and 5.54 (95% CI: 2.69 – 11.40), for the first and second analyses, respectively. Conclusion: R-CHOP and R-CVP protocols achieve excellent overall response. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive CR rate. In younger patients with FL where cumulative cardio-toxicity may be of importance in the long term and in whom future stem cell transplantation is an option, again R-CVP may be a more appealing option. http://www.jhoonline.org/content/2/1/14 Siddhartha Ganguly Vijay Patel Journal of Hematology & Oncology 2009, null:14 2009-03-24T00:00:00Z doi:10.1186/1756-8722-2-14 /content/figures/1756-8722-2-14-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 14 2009-03-24T00:00:00Z XML Although the majority of published cases of lead poisoning come from occupational exposures, some traditional remedies may also contain toxic amounts of lead. Ayurveda is a system of traditional medicine that is native to India and is used in many parts of world as an alternative to standard treatment regimens. Here, we report the case of a 58-year-old woman who presented with abdominal pain, anemia, liver function abnormalities, and an elevated blood lead level. The patient was found to have been taking the Ayurvedic medicine Jambrulin prior to presentation. Chemical analysis of the medication showed high levels of lead. Following treatment with an oral chelating agent, the patient's symptoms resolved and laboratory abnormalities normalized. This case highlights the need for increased awareness that some Ayurvedic medicines may contain potentially harmful levels of heavy metals and people who use them are at risk of developing associated toxicities. http://www.jhoonline.org/content/4/1/51 Krishna Gunturu Priyadharsini Nagarajan Peter McPhedran Thomas Goodman Michael Hodsdon Matthew Strout Journal of Hematology & Oncology 2011, null:51 2011-12-20T00:00:00Z doi:10.1186/1756-8722-4-51 /content/figures/1756-8722-4-51-toc.gif Journal of Hematology & Oncology 1756-8722 ${item.volume} 51 2011-12-20T00:00:00Z XML